Usefulness of administrative databases in identifying the predictive factors of repeated hospitalizations for heart failure.

OBJECTIVES: to investigate heart failure (HF) hospitalizations, the following one-year follow-up, and any possible connection between rehospitalizations due to HF and patients' characteristics derived from administrative databases. DESIGN: retrospective longitudinal design. SETTING AND PARTICIPANTS: the study was conducted analyzing public hospital records of a district in Abruzzo Region (Central Italy), which counts more than 300,000 inhabitants. Patients hospitalized for HF from 01.01.2016 to 31.12.2017 (index event) were included in the study and followed-up for one year. MAIN OUTCOME MEASURES: frequency of repeated hospital admissions, time intervals from the index HF hospitalizations, and causes of readmissions were investigated. RESULTS: a total of 1,587 patients discharged alive after an index hospitalization for HF were included in the study. The mean age of the patients was 79.6 years and the majority of them were females (53.7%). The mean length of stay (LOS) for the index hospitalizations was 8.8 ±6.8 days. During the follow-up period, 336 (21.2%) patients underwent one to four repeated hospitalizations for HF. The first readmission due to HF occurred after a median time of 106.5 days from the index event discharge, and for 20.0% of all cases it occurred within 31 days; 453 patients (28.6%) were readmitted exclusively for other causes, and 67 (4.2%) died out of hospital without any previous HF re-hospitalization. When the outcome was considered as a composite endpoint (out-of-hospital death/HF re-hospitalization), age >=75 (HR 1.737; 95%CI 1.330-2.267), LOS at the index hospitalization >=8 days (HR 1.302; 95%CI 1.066-1.591), and repeated hospitalizations for other causes (HR 1.789; 95%IC 1.465-2.185) were associated with the risk of repeated hospitalizations for HF. CONCLUSIONS: this study shows that about one HF patient out of five experienced at least one re-hospitalization for HF within one year from index hospitalization. In addition to having a longer index hospitalization, these patients were older and frequently suffered from comorbidities which also led to hospitalizations. The results underline the need for a close and careful follow-up after the discharge of old HF patients with multiple pathologies in order to avoid further HF admissions in a short time.

Physical Activity Modulates the Overexpression of the Inflammatory miR-146a-5p in Obese Patients.

Specific microRNAs (miRs), including the "angio-miR-126" and the "inflamma-miR-146a-5p," have been proposed as biomarkers and even therapeutic targets of obesity-associated metabolic diseases. Physical activity, a key measure of prevention for obesity and its complications, is reported to influence the expression of these miRs. In this study, we investigate whether a physical activity program proven to improve metabolic parameters in obese patients can correct the circulating levels of these miRs. Plasma miR-126 and miR-146a-5p were measured in a cohort of obese patients (n = 31, 16F + 15M) before and after the 3-month physical activity program of the CURIAMO trial (registration number for clinical trials: ACTRN12611000255987) and in 37 lean controls (24F + 13M). miR-146a-5p, but not miR-126, was significantly increased in obese patients as compared with lean controls and decreased in approximately two-thirds of the participants post-intervention with a response that positively correlated with pre-intervention levels of this miR. Waist circumference, the inflammatory cytokine IL-8 and lipid parameters, principally total cholesterol, showed the strongest correlation with both the baseline levels and post-intervention correction of miR-146a-5p. Post-hoc analysis of experimental data supports the use of miR-146a-5p as a biomarker and predictor of the clinical response to physical activity in obese patients. Furthermore, miR-146a-5p expression was confirmed to increase together with that of the inflammatory genes TLR4, NF-κB, IL-6, and TNF-α in LPS-stimulated human mononuclear leukocytes. In conclusion, the inflamma-miR-146a-5p can serve as a personalized predictor of clinical outcome in obese patients entering physical activity weight-reduction programs. © 2018 IUBMB Life, 70(10):1012-1022, 2018.

Oscillating glucose induces microRNA-185 and impairs an efficient antioxidant response in human endothelial cells.

BACKGROUND: Intracellular antioxidant response to high glucose is mediated by Cu/Mn-superoxide dismutases (SOD-1/SOD-2), catalase (CAT) and glutathione peroxidases (GPx), particularly glutathione peroxidase-1 (GPx-1). Although oscillating glucose can induce a more deleterious effect than high glucose on endothelial cells, the mechanism by which oscillating glucose exerts its dangerous effects is incompletely understood; however, the involvement of oxidative damage has been generally accepted. In this study we sought to determine whether oscillating glucose differentially modulates antioxidant response, and to elucidate the potential regulatory mechanisms exerted by the microRNA-185 (miR-185). METHODS: Human endothelial cells were exposed for 1 week to constant and oscillating high glucose. SOD-1, SOD-2, CAT and GPx-1, as well as two markers of oxidative stress [8-hydroxy-2'-deoxyguanosine (8-OHdG) and the phosphorylated form of H2AX (γ-H2AX)] were measured at the end of the experiment. Intracellular miR-185 was measured and loss-of function assays were performed in HUVEC. Bioinformatic tool was used to predict the link between miR-185 on 3'UTR of GPx-1 gene. Luciferase assay was performed to confirm the binding on HUVEC. RESULTS: After exposure to constant high glucose SOD-1 and GPx-1 increased, while in oscillating glucose SOD-1 increased and GPx-1 did not. SOD-2 and CAT remained unchanged under both conditions. A critical involvement of oscillating glucose-induced miR-185 in the dysregulation of endogenous GPx-1 was found. Computational analyses predict GPx-1 as miR-185's target. HUVEC cultures were used to confirm glucose's causal role on the expression of miR-185, its target mRNA and protein and finally the activation of antioxidant response. In vitro luciferase assays confirmed computational predictions targeting of miR-185 on 3'-UTR of GPx-1 mRNA. Knockdown of miR-185, using anti-miR-185 inhibitor, was accompanied by a significant upregulation of GPx-1 in oscillating glucose. 8-OHdG and γ-H2AX increased more in oscillating glucose than in constant high glucose. CONCLUSIONS: Glucose oscillations may exert more deleterious effects on the endothelium than high glucose, likely due to an impaired response of GPx-1, coupled by the upregulation of miR-185.

Short-term high glucose exposure impairs insulin signaling in endothelial cells.

BACKGROUND: Hyperglycemia is the hallmark of diabetes and its cardiovascular complications. Insulin plays an important role in the regulation of vascular homeostasis and maintenance of endothelial function. Insulin signaling occurs after binding to the insulin receptor, causing activation of two separate and parallel pathways: PI3K/AKT/eNOS and Ras/Raf/MAPK pathways. AKT phosphorylates eNOS at Ser1177, resulting in increased nitric oxide production and vasodilation. The MAPK pathway results in endothelin-1 production and vasoconstriction and mitogenic effects. METHODS: We studied the effects of physiological insulin treatment in human umbilical vein endothelial cells (HUVECs) on the two pathways under high glucose conditions, which mimic the in vivo condition of hyperglycemia. HUVECs were incubated with insulin at different physiological concentrations (from 10(-10) to 10(-8) M) for 30 min after 24 h of exposition to normal (5 mmol/L, NG) or high glucose (25 mmol/L, HG). Phosphorylated forms of AKT, eNOS, ERK1/2, p38, JNK and insulin receptor-ß subunit (IRß) were evaluated. RESULTS: In normal glucose, the active phosphorylated forms of AKT, eNOS, ERK1/2, p38 and JNK were increased in insulin treated cells, in a dose-dependent manner. In high glucose, insulin was not able to activate the PI3K/AKT/eNOS pathway, with the phosphorylated form of eNOS reduced with respect to the control. However, insulin was able to induce the up-regulation of phospho-ERK1/2, -p38 and -JNK. Moreover, we found reduced levels of IRß phosphorylated form in high glucose as compared to the control. Insulin was able to increase phospho-IRß in normal glucose but not in high glucose, in which the total protein levels remained reduced. CONCLUSIONS: Exposure to short-term high glucose negatively affects insulin signaling even when physiological insulin concentrations are added. The impairment of the PI3K/AKT/eNOS pathway after physiological insulin treatment could contribute to detrimental effects on cardiovascular homeostasis under high glucose conditions, and might shift toward the activation of certain mitogenic effectors, such as ERK1/2, p38 and JNK, the only ones that respond to physiological insulin treatment in high glucose.

Therapeutic management of chronic hepatitis B in clinical practice: a region-wide survey.

GOALS: To characterize the clinical and treatment pattern in a large population of hepatitis B virus (HBV) patients managed at tertiary referral centers in clinical practice. BACKGROUND: Successful treatment, either with interferon (IFN) or nucleos(t)ide analogs (NUCs), of chronic HBV infection is associated with improved long-term patient outcome. However, in clinical practice, the actual management of these patients is not well characterized, and data regarding treatment pattern in this setting are lacking. METHODS: In this cross-sectional study, we evaluated 505 patients chronically infected with HBV alone and who had at least 1-year follow-up. We assessed indication to, rate of, and type of treatment as well as the characteristics of treated patients. RESULTS: Overall prevalence of positivity for HBe antigen was 19.3%, and the majority of patients had chronic hepatitis (47.5%). Non-Italian patients represented approximately one third of the population (27.1%). Among patients with indication to antiviral therapy (n=318), treatment was actually carried out in 264 patients (83.0%), prevalently with NUCs (65.9%). IFN-treated patients were younger (P<0.001), more frequently male (P=0.025) and HBeAg positive (P=0.003), and less frequently cirrhotics (P<0.001) as compared with patients treated with NUCs. CONCLUSIONS: In a geographical area with a low positivity for HBe antigen, antiviral therapy is actually carried out in the majority of patients who have indication to treatment, prevalently with NUCs, whereas IFN treatment is more frequently carried out in young, HBe antigen-positive patients who do not have advanced liver disease.

The protective effect of the Mediterranean diet on endothelial resistance to GLP-1 in type 2 diabetes: a preliminary report.

BACKGROUND: In type 2 diabetes, acute hyperglycemia worsens endothelial function and inflammation,while resistance to GLP-1 action occurs. All these phenomena seem to be related to the generation of oxidative stress. A Mediterranean diet, supplemented with olive oil, increases plasma antioxidant capacity, suggesting that its implementation can have a favorable effect on the aforementioned phenomena. In the present study, we test the hypothesis that a Mediterranean diet using olive oil can counteract the effects of acute hyperglycemia and can improve the resistance of the endothelium to GLP-1 action. METHODS: Two groups of type 2 diabetic patients, each consisting of twelve subjects, participated in a randomized trial for three months, following a Mediterranean diet using olive oil or a control low-fat diet. Plasma antioxidant capacity, endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels were evaluated at baseline and at the end of the study. The effect of GLP-1 during a hyperglycemic clamp, was also studied at baseline and at the end of the study. RESULTS: Compared to the control diet, the Mediterranean diet increased plasma antioxidant capacity and improved basal endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels. The Mediterranean diet also reduced the negative effects of acute hyperglycemia, induced by a hyperglycemic clamp, on endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels. Furthermore, the Mediterranean diet improved the protective action of GLP-1 on endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels, also increasing GLP-1-induced insulin secretion. CONCLUSIONS: These data suggest that the Mediterranean diet, using olive oil, prevents the acute hyperglycemia effect on endothelial function, inflammation and oxidative stress, and improves the action of GLP-1, which may have a favorable effect on the management of type 2 diabetes, particularly for the prevention of cardiovascular disease.

Nutritional imbalances linking cellular senescence and type 2 diabetes mellitus.

PURPOSE OF REVIEW: Quality of nutrition plays a central role in illnesses such as diabetes and its complications. Dietary and lifestyle habits may have a strong impact, either worsening or improving the evolution of diabetes mellitus. Some factors, such as obesity, worsen the illness, causing chronic inflammation, lipid metabolic disorder, accelerated atherosclerosis, increased risk for thrombosis, hypertension, hyperinsulinemia, insulin resistance, and cellular senescence. Some other nutritional components, however, have an opposite effect, probably increasing antioxidant defense. RECENT FINDINGS: The effects of nutritional factors on cellular senescence in diabetic patients are described in this review. In particular, we discuss some of the nutritional causes of cellular senescence in diabetes mellitus and focus on different nutraceutical compounds that can affect cellular senescence. Furthermore, relevant mechanisms of action are also described. SUMMARY: Diet and nutraceutical factors have important effects on diabetes mellitus. Some molecules, which improve antioxidant defense, may counteract cellular senescence. A good lifestyle with physical activity and good weight control can improve the quality of life in diabetic people; on the contrary, obesity and vitamin deficiencies may worsen the evolution of this illness, even inducing cellular senescence.

Evidences of +896 A/G TLR4 polymorphism as an indicative of prevalence of complications in T2DM patients.

T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication's prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P = 0.026), lower limb arteriopathy (P = 0.013), and the major cardiovascular pathologies (P = 0.017). Their cumulative risk was significant (P = 0.01), with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642-8.741). Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients.

Chronic renal impairment and DDAH2-1151 A/C polymorphism determine ADMA levels in type 2 diabetic subjects.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). Increased levels of ADMA cause impaired vasodilation, leading to endothelial dysfunction and a higher risk for cardiovascular events. In patients with a chronic kidney disease, increased ADMA levels are reported to play a role in the pathogenesis of accelerated atherosclerosis and are an independent risk marker leading to end-stage renal disease and mortality. Circulating ADMA is metabolized by the action of dimethylarginine dimethylamino hydrolase (DDAH) and DDAH2 isoform is the most prevalent in tissues expressing endothelial NOS. DDAH and NOS are co-expressed in the same kidney regional sites supporting the hypothesis that a strict and specific regulation of intracellular ADMA levels is crucial for NO generation in the kidney. Starting from these findings, the study aims to investigate the role of DDAH2 gene promoter polymorphism at position -1151 A/C in determining the levels of ADMA in type 2 diabetic patients (T2DM) with chronic renal impairment. METHODS: Three groups of carefully selected subjects of both sexes were enrolled and compared. The first group (control subjects) comprised 286 non-diabetic subjects (mean age 55.8 ± 11.4 years), the second group (T2DM uncomplicated subjects) was made up of 322 T2DM subjects without complications (mean age 64.9 ± 9.6 years) whereas the third group (T2DM CRF subjects) included 110 T2DM patients with chronic renal impairment. The rs805304 DDAH2-1151 A/C promoter polymorphism was determined by a polymerase chain reaction-restriction fragment length polymorphism approach. Results T2DM CRF subjects showed significant increased plasma levels of ADMA with respect to those of T2DM uncomplicated subjects and control subjects (0.51 versus 0.39 versus 0.37 µmol/L, P = 0.002, respectively). Analysis of variance showed an interaction between DDAH2-1151 C carrier and groups on ADMA plasma levels (F = 4.36; P < 0.05). ADMA plasma levels were also dependent on groups (F = 4.96; P < 0.01). CONCLUSIONS: Our work demonstrates that rs805304 DDAH2-1151 polymorphism plays a central role in determining ADMA in diabetic renal impairment, where patients with DDAH2-1151 C carriers showed the highest ADMA levels. This unfavourable genetic profile is highlighted by pathological kidney conditions such as diabetic CRF. These findings could open new insights on the pathways involving ADMA/DDAH/NOS in the development and progression of chronic renal impairment and therefore of the other micro- macrovascular diabetic complications.

Abdominal radical trachelectomy: a safe and feasible option for fertility preservation in developing countries.

OBJECTIVE: This study aimed to report on a series of patients with early-stage cervical cancer who underwent an abdominal radical trachelectomy to preserve their fertility. MATERIALS AND METHODS: We performed a retrospective review of all patients who underwent an abdominal radical trachelectomy in 2 centers of gynecologic oncology in Argentina. Data collected included patient's age, stage, histologic subtype, tumor grade, tumor size, evidence of lymph vascular space invasion, number of lymph nodes removed, perioperative complications, as well as oncologic and obstetrical outcomes. RESULTS: Thirty patients were selected for radical trachelectomy. Five of these patients were excluded from the study: 3 for compromised margins, 1 for lymph node involvement, and 1 for vesicovaginal space involvement. Twenty-five patients underwent the procedure and were included in this report. Median age was 31 years (range = 22-40 years). Nineteen patients had stage IB1, and 6 patients had stage IA2 cervical cancer. Median tumor size was 1.2 cm (range = 0.4-3.5 cm). Median number of pelvic lymph nodes removed was 21 (range = 11-33). Median surgical time was 240 minutes (range = 210-270 minutes), and median length of hospital stay was 3.5 days (range = 3-5 days). Estimated blood loss was 350 mL (range = 200-700 mL). No intraoperative complications were reported. There were 6 postoperative complications. Three patients (12%) were able to get pregnant spontaneously with 3 live births by cesarean delivery. No recurrences were reported with a median follow-up of 29.6 months. CONCLUSIONS: Abdominal radical trachelectomy with pelvic lymphadenectomy is a feasible procedure and a viable option for women wishing to preserve their fertility in developing countries.

Safety and efficacy of direct oral anticoagulants in geriatric patients with non-valvular atrial fibrillation: A single-center retrospective study.

INTRODUCTION: Direct oral anticoagulants (DOACs) are widely employed for antithrombotic prophylaxis in patients with atrial fibrillation (AF). However, there is still uncertainty about their risk-benefit profile in older patients. Here, we evaluated the efficacy, safety, and dose appropriateness of DOACs in a real-world population of outpatients with non-valvular AF, with a specific focus on subjects aged over 80 years and/or with reduced renal function. MATERIALS AND METHODS: Single-center retrospective study including patients who had been prescribed a DOAC between May 2014 and May 2021 for long-term anticoagulation in non-valvular AF. Patients anticoagulated for <4 weeks were excluded. The primary efficacy outcome was a composite of cardiovascular (CV) death, stroke, or systemic embolism. The primary safety outcome was major bleeding. RESULTS: A total of 1154 patients (median age 84 yrs., range 57-100 yrs.), among which 862 were 80 years and older, were included. In the subgroup of subjects ≥80 yrs., a subtherapeutic dose of DOAC was associated with an increased incidence of CV mortality, stroke, or systemic embolism (multivariable Cox regression, HR = 2.09, 95 % CI: 1.09-4.02), with no benefit in terms of prevalence of bleeding events (21.5 % vs. 18.6 %, p = 0.428), and the incidence of adverse safety and efficacy outcomes was not increased in patients with a reduced renal function (eGFR ≤30 mL/min). Plasma concentration of DOACs, assessed in a subset of 367 patients, did not increase with advanced age (≥ 80 yrs., two-way ANOVA, p = 0.656) nor with declining eGFR (≤30 mL/min, two-way ANOVA, p = 0.643) and was not associated with adverse safety and efficacy outcomes. CONCLUSIONS: Data from our study support the use of DOACs in populations of older adults and remark on the risks associated with inappropriate prescriptions in terms of CV mortality and adverse events.

[Predictors of clinical response in patients with ulcerative colitis treated with granulocyte-monocyte apheresis: analysis of the apheresis registry data]. / Predittori di risposta clinica in pazienti affetti da colite ulcerosa trattati con granulocito-monocito aferesi: analisi dei dati del registro aferesi.

We analyzed predictors of clinical response after a cycle of granulocytemonocyte apheresis in 173 patients with ulcerative colitis. Hemoglobin levels independently predicted good clinical outcome.

The Genetic Variability of Members of the SLC38 Family of Amino Acid Transporters (SLC38A3, SLC38A7 and SLC38A9) Affects Susceptibility to Type 2 Diabetes and Vascular Complications.

Type 2 Diabetes (T2D) is a metabolic disease associated with long-term complications, with a multifactorial pathogenesis related to the interplay between genetic and modifiable risk factors, of which nutrition is the most relevant. In particular, the importance of proteins and constitutive amino acids (AAs) in disease susceptibility is emerging. The ability to sense and respond to changes in AA supplies is mediated by complex networks, of which AA transporters (AATs) are crucial components acting also as sensors of AA availability. This study explored the associations between polymorphisms in selected AATs genes and T2D and vascular complications in 433 patients and 506 healthy controls. Analyses revealed significant association of SLC38A3-rs1858828 with disease risk. Stratification of patients based on presence/absence of vascular complications highlighted significant associations of SLC7A8-rs3783436 and SLC38A7-rs9806843 with diabetic retinopathy. Additionally, the SLC38A9-rs4865615 resulted associated with chronic kidney disease. Notably, these genes function as AAs sensors, specifically glutamine, leucine, and arginine, linked to the main nutrient signaling pathway mammalian target of rapamycin complex 1 (mTORC1). Thus, their genetic variability may contribute to T2D by influencing the ability to properly transduce a signal activating mTORC1 in response to AA availability. In this scenario, the contribution of dietary AAs supply to disease risk may be relevant.

Mass spectrometry measurement of plasma hepcidin for the prediction of iron overload.

BACKGROUND: Hepcidin has emerged as the primary regulator of iron homeostasis. Previous studies on assessing urinary hepcidin are limited. We developed a method for quantifying hepcidin-25 (Hep-25) in plasma using surface-enhanced laser-desorption-ionization time-of-flight mass spectrometry (SELDI-TOF/MS) and a 25-AA peptide as reference standard. The aims of the study were 1) to assess the performance of this method in different conditions of iron metabolism disorders; 2) to assess the diagnostic validity of non-invasive serum biomarkers in the identification of iron overload. METHODS: Validation of the method was performed in 10 patients with type I hemochromatosis (HE) and in 177 subjects previously enrolled in a general population epidemiological study. Among the latter group, 17 had non-alcoholic fatty liver disease, 10 had chronic hepatitis C, and 150 subjects had normal ultrasound, normal liver function tests (LFTs), an alcohol intake < 20 g ethanol/day and were negative for the C282Y mutation. The following biomarkers were assayed in each case: plasma Hep-25, C282Y and H63D mutations of the HFE gene; serum iron, ferritin (SF), transferrin saturation, transaminases, γ-glutamyltransferase (GGT), glucose, insulin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. RESULTS: Plasma Hep-25 concentrations were higher in HCV+ patients (26.3 ± 7.2 nmol/L) than in controls, and correlated positively with SF (p < 0.001). H63D heterozygous subjects revealed a pattern of iron overload that was significantly higher than H63D wild type subjects. Analyzing the data with the Biomarker Pattern 5.0.2. software to identify the most significant biomarkers for discriminating between HE cases and controls allowed us to produce an algorithm with four terminal nodes, which included glucose > 4.8 mmol/L and Hep-25/SF ratio ≤ 6.6 as the main splitters. These variables enabled the correct diagnosis of HE with 100% sensitivity, 93% specificity and an area under the receiver operating characteristic (ROC) curve of 0.993. CONCLUSIONS: Our plasma Hep-25 mass spectrometry method yields measurements that reflect pathological and genetic influences; simple non-invasive biomarkers (Hep-25/SF ratio and glucose) can predict the presence of HE.

The Italian Registry of Therapeutic Apheresis: granulocyte-monocyte apheresis in the treatment of inflammatory bowel disease. A multicentric study.

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte-monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohn's disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn's disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered.

Initial experience in a vulvovaginal aesthetic surgery unit within a general gynecology department.

OBJECTIVE: To evaluate what the appropriate indications are for vulvovaginal (VV) plastic surgeries in our environment. MATERIALS AND METHODS: This is a retrospective study of 73 consecutive patients who were seen on consultation at the gynecologic aesthetic unit between January 2008 and January 2009 asking for a VV aesthetic surgery.All patients completed the Female Sexual Function Index questionnaire and received information on sexuality. RESULTS: Of the 73 patients seen on consultation, 32 (43.8%) underwent surgery, and the main reason for this was reduction labioplasty in 19 patients, widening vaginoplasty in 6, reduction vaginoplasty in 1, and resection of asymmetries in 6 patients. None of the patients seen on consultation for vulvar bleaching, G-spot amplification, or augmentation labioplasty underwent surgery. Postoperative complications included wound dehiscence in 3 patients (9.3%) and a vulvar hematoma in 1 patient (3.1%).Postoperative sexual satisfaction was optimal for 30 patients; only 2 complained of dyspareunia. CONCLUSIONS: Most patients seen on consultation for VV plastic surgery had no need for it and only received information regarding female anatomy and sexuality. Reduction labioplasty owing to hypertrophy of the labia minora represented the most frequent reason for consultation and surgery. Indications for VV plastic surgeries should be based not only on surgical results but also on the reported satisfaction achieved by those patients who did not undergo surgery and only received appropriate information during consultation.

Author Correction: Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A simple approach for mouse embryonic stem cells isolation and differentiation inducing embryoid body formation.

Stem cells were derived from hatched blastocyst-stage mouse embryos of the C57BL/6 strain employing a knockout serum replacement instead of the traditional fetal calf serum, thereby avoiding the use of immunosurgery. Although fetal calf serum was not good for isolation of stem cells, a combination of this serum plus knockout serum increased the expansion rate of the cell culture. The derived cells were capable of maintaining an undifferentiated state during several passages, as demonstrated by the presence of alkaline phosphatase activity, stage-specific embryonic antigen 1 (SSEA-1), and octamer binding protein 4 (Oct-4). Suspension culture in bacteriological dishes gave better results than the hanging drop method for differentiation by means of embryoid body formation. Mouse embryonic stem cells showed spontaneous differentiation into derivatives of the 3 germ layers in culture media supplemented with fetal calf serum but not with knockout serum.