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.

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.

Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages.

Diabetic status is characterized by chronic low-grade inflammation and an increased burden of senescent cells. Recently, the senescence-associated secretory phenotype (SASP) has been suggested as a possible source of inflammatory factors in obesity-induced type 2 diabetes. However, while senescence is a known consequence of hyperglycaemia, evidences of SASP as a result of the glycaemic insult are missing. In addition, few data are available regarding which cell types are the main SASP-spreading cells in vivo. Adopting a four-pronged approach we demonstrated that: i) an archetypal SASP response that was at least partly attributable to endothelial cells and macrophages is induced in mouse kidney after in vivo exposure to sustained hyperglycaemia; ii) reproducing a similar condition in vitro in endothelial cells and macrophages, hyperglycaemic stimulus largely phenocopies the SASP acquired during replicative senescence; iii) in endothelial cells, hyperglycaemia-induced senescence and SASP could be prevented by SOD-1 overexpression; and iiii) ex vivo circulating angiogenic cells derived from peripheral blood mononuclear cells from diabetic patients displayed features consistent with the SASP. Overall, the present findings document a direct link between hyperglycaemia and the SASP in endothelial cells and macrophages, making the SASP a highly likely contributor to the fuelling of low-grade inflammation in diabetes.

Physical activity and progenitor cell-mediated endothelial repair in chronic heart failure: Is there a role for epigenetics?

Chronic heart failure (CHF) is the most common cardiac disease among the elderly and a leading cause of mortality in elderly patients. Endothelial dysfunction is held to have a major role in the development and progression of CHF, which results in progressively impaired functional capacity. Endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs) are the main players involved in the endogenous repair mechanisms that can counteract endothelial dysfunction. A mounting body of data indicates that exercise enhances endothelial renewal through mobilization of bone marrow-derived EPCs and CACs, making it an effective therapeutic tool for CHF. Interestingly, emerging evidence has been showing that exercise training can also promote epigenetic modifications, e.g. DNA methylation, histone modifications, and differential expression of specific non-coding RNAs like microRNA (miRNAs). Since deregulation of the miRNAs involved in endothelial function modulation has widely been documented in circulating cells and plasma of CHF patients, deregulation of epigenetic features could play a key role in disease progression. Here, we review current knowledge of the contribution of EPCs and CACs to endothelial repair mechanisms in CHF patients, focusing on the effects induced by exercise training and hypothesizing that some of these effects can be mediated by epigenetic mechanisms.

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.

Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes.

The development of type-2 diabetes mellitus (T2DM) and its complications is largely due to the complex interaction between genetic factors and environmental influences, mainly dietary habits and lifestyle, which can either accelerate or slow down disease progression. Recent findings suggest the potential involvement of epigenetic mechanisms as a crucial interface between the effects of genetic predisposition and environmental factors. The common denominator of environmental factors promoting T2DM development and progression is that they trigger an inflammatory response, promoting inflammation-mediated insulin resistance and endothelial dysfunction. Proinflammatory stimuli, including hyperglycemia, oxidative stress, and other inflammatory mediators, can affect epigenetic mechanisms, altering the expression of specific genes in target cells without changes in underlying DNA sequences. DNA methylation and post-translational histone modifications (PTHMs) are the most extensively investigated epigenetic mechanisms. Over the past few years, non-coding RNA, including microRNAs (miRNAs), have also emerged as key players in gene expression modulation. MiRNAs can be actively released or shed by cells in the bloodstream and taken up in active form by receiving cells, acting as efficient systemic communication tools. The miRNAs involved in modulation of inflammatory pathways (inflammamiRs), such as miR-146a, and those highly expressed in endothelial lineages and hematopoietic progenitor cells (angiomiRs), such as miR-126, are the most extensively studied circulating miRNAs in T2DM. However, data on circulating miRNA signatures associated with specific diabetic complications are still lacking. Since immune cells and endothelial cells are primarily involved in the vascular complications of T2DM, their relative contribution to circulating miRNA signatures needs to be elucidated. An integrated approach encompassing different epigenetic mechanisms would have the potential to provide new mechanistic insights into the genesis of diabetes and its severe vascular complications and identify a panel of epigenetic markers with diagnostic/prognostic and therapeutic relevance.

Laparoscopic radical trachelectomy: technique, feasibility, and outcomes.

BACKGROUND AND OBJECTIVES: Our objectives are to describe our surgical technique for laparoscopic radical trachelectomy, to evaluate its feasibility, and to present the perioperative results at Hospital Italiano de Buenos Aires, Argentina. METHODS: We analyzed 4 patients who underwent laparoscopic radical trachelectomy for early-stage cervical cancer between December 2011 and May 2013. RESULTS: Four patients were included in this study. Total laparoscopic radical trachelectomy was performed in all cases. The mean age was 26 years (range, 19-32 years), the mean body mass index was 21 (range, 18-23), and the mean length of hospital stay was 33 hours (range, 24-36 hours). The mean operative time was 225 minutes (range, 210-240 minutes), and no complications were reported. During the postoperative period, only 1 patient presented with left vulvar edema, which resolved spontaneously. The pelvic and parametrial lymph nodes, as well as the vaginal cuff and cervical resection margins, were negative for malignancy in all cases. On average, 18 pelvic lymph nodes (range, 15-20) were removed. The tumor stage was IB in all 4 patients, and the mean tumor size was 17 mm (range, 12-31 mm). No patient required conversion to laparotomy. CONCLUSION: We consider laparoscopic radical trachelectomy, performed by trained surgeons, a feasible and safe therapeutic option as a fertility-sparing surgical technique, with good perioperative outcomes for women with early-stage cervical cancer with a desire to preserve their fertility. Minimally invasive surgery provides the widely known benefits of this type of approach.

Serum levels of adipocytokines in psoriasis patients receiving tumor necrosis factor-α inhibitors: results of a retrospective analysis.

BACKGROUND: Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases. OBJECTIVES: This study was conducted to evaluate the effects of tumor necrosis factor-α (TNF-α) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis. METHODS: Serum levels of adiponectin, resistin, visfatin, leptin, TNF-α, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF-α inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits. RESULTS: At baseline, mean serum levels of TNF-α, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P < 0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P < 0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P > 0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P < 0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an anti-inflammatory adipocytokine, were only mildly increased and persisted at a significantly lower level than in healthy controls (P > 0.005). CONCLUSIONS: Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF-α inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines.

Simultaneous GLP-1 and insulin administration acutely enhances their vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes.

OBJECTIVE: To test the hypothesis that the simultaneous administration of GLP-1 and insulin may increase their vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes. RESEARCH DESIGN AND METHODS: In two groups of persons with type 2 diabetes, two sets of experiments were performed. The first group had two normoglycemic-normoinsulinemic clamps with or without GLP-1 and two normoglycemic-hyperinsulinemic clamps with or without GLP-1. The second group had two hyperglycemic-normoinsulinemic clamps and two hyperglycemic-hyperinsulinemic clamps with or without GLP-1. RESULTS: During the normoglycemic-hyperinsulinemic clamp, flow-mediated dilatation (FMD) increased, while soluble intercellular adhesion molecule (sICAM-1), plasma 8-iso-prostaglandin F2α (8-iso-PGF2α), nitrotyrosine, and interleukin (IL)-6 decreased compared with normoglycemic-normoinsulinemic clamp. Similar results were obtained with the infusion of GLP-1 during the normoglycemic-normoinsulinemic clamp. The combination of hyperinsulinemia and GLP-1 in normoglycemia was accompanied by a further FMD increase and sICAM-1, 8-iso-PGF2α, nitrotyrosine, and IL-6 decrease. During the hyperglycemic-normoinsulinemic clamp, FMD significantly decreased, while sICAM-1, 8-iso-PGF2α, nitrotyrosine, and IL-6 significantly increased. When hyperglycemia was accompanied by hyperinsulinemia or by the simultaneous infusion of GLP-1, these phenomena were attenuated. The simultaneous presence of hyperinsulinemia and GLP-1 had an increased beneficial effect. CONCLUSIONS: Our results show that the combination of insulin and GLP-1 is more effective than insulin or GLP-1 alone in improving endothelial dysfunction, inflammation, and oxidative stress in type 2 diabetes.

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.

The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study.

Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin (ß = -1.27; p = 0.001) and HOMA-IR (ß = -0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.

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.

Carcinoma ductal in situ: experiencia del SGHI de Buenos Aires / Ductal carcinoma in situ: experience of the SGHI in Buenos Aries

El carcinoma ductal in situ de la mama (CDIS), representa una prolifereción de células anormales confinadas a los conductos de la mama y es un factor de riesgo para desarrollar cáncer de mama invasor. El diagnóstico del CDIS ha aumentado considerablemente a través del tiempo, a partir del uso rutinario de la mamografía en 1980. Existen controversias con relación al tratamiento óptimo luego de la cirugía (cuadrantectomía o mastectomía).

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.

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.

Evaluation of laparoscopic management of gynecologic emergencies by residents.

OBJECTIVE: To evaluate the feasibility of laparoscopic management of women with gynecologic emergencies by the residents and the chief resident in an organized resident training program. METHODS: A retrospective study of patients with gynecologic emergencies who underwent laparoscopic surgery between January 1, 1999, and May 31, 2006 was done. RESULTS: For the 369 patients included, the mean operative time of 74±31.35 minutes was significantly increased by advanced patient age (P<0.001), pelvic inflammatory disease with or without tubo-ovarian abscess (PID±TOA) (P<0.050), the first semester of chief residency (P<0.050), and conversion to laparotomy (P<0.001). Mean length of hospital stay was 40±24 hours. Factors such as advanced patient age (P<0.001), prolonged length of surgery (P<0.001), PID±TOA (P<0.001), first semester of chief residency (P<0.050), conversion to laparotomy (P<0.001), and blood transfusion (P<0.050) significantly increased the length of hospital stay. The conversion rate to laparotomy was 4.6% (n=17), and it was significantly associated with advanced women age (OR 1.11; 95% CI, 1.05-1.17, P<0.001) and PID±TOA (OR 6.04; 95%CI, 2.17-16.62, P<0.001). Postoperative complications were recorded in 3 (0.81%) patients. CONCLUSION: Laparoscopic management of gynecologic emergencies by senior residents and a chief resident within an organized resident training program is feasible. These results reinforce the relevance of a well-structured residency endoscopic training program.

The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI-1 plasma levels in ageing.

Plasminogen activator inhibitor 1 (PAI-1) is over-expressed during ageing and it has been linked to cellular senescence. Recently, PAI-1 has been also identified in vitro as a critical downstream target of p53. TP53, the p53 gene, has a common functional polymorphism at codon 72 which influences the capability to modulate both apoptosis and cell senescence. In the attempt to demonstrate an in vivo role of p53 in the relationship between PAI-1 and age, we studied PAI-1 on 570 healthy subjects (aged from 18 to 92yrs.). PAI-1 showed significant relationship with age (r=0.12, p=0.02). Stratifying by genotype, it became evident that the association between PAI-1 and age was mainly due to Pro/Pro subjects (partial r=0.75, p<0.01). These results have been confirmed by a validation study on an independent sample population of 496 subjects (aged from 18 to 94yrs.). This is the first demonstration of an in vivo role of TP53 polymorphism in PAI-1 regulation, supporting the hypothesis that the effects of this polymorphism are age-dependent. In particular, our results indicate that Pro/Pro genotype plays a pivotal role in determining PAI-1 levels in aged subjects, while in Arg carriers PAI-1 levels are associated to the known insulin related determinants.

Right atrial hemangioma.

Hemangiomas are rare benign neoplasms of the heart generally diagnosed in young or middle-aged patients. We report a case of asymptomatic 71-year-old-woman in whom the tumor was detected after an echocardiogram. Echocardiography directs the diagnosis toward a cardiac mass but some aspects can suggest the hemangioma; MRI and coronary arteriography establishes the diagnosis showing the typical tumor blush.