Carbon and nitrogen isotopic similarity between the endangered Darwin's fox (Lycalopex fulvipes) and sympatric free-ranging dogs in Chiloé Island, Chile.

Darwin's fox is an opportunistic omnivorous predator native to Chile classified as endangered by the IUCN Red List. Habitat use by Darwin's foxes can be negatively affected by the presence of free-ranging dogs that range freely across native and non-native habitats and can be a source of fox mortality. The objective of this study was to analyze the isotopic similarity of Darwin's fox and sympatric free-ranging dogs in Chiloé Island to determine the impact of anthropogenic environmental alterations on wild predators. We use hair samples to characterise and compare their δ13C and δ15N values and to evaluate isotopic similarity and isotope niches overlap. A generalised linear model was used to associate the isotope value with landscape variables (forest cover and vegetation type) and distance to the nearest house. We found no significant differences in δ13C or δ15N values between foxes and dogs, and a marginally significant isotope niche overlap (59.4 %). None of the selected variables at landscape and site scale were related to isotope values. Although our study is not a probe of direct contact between foxes and free-ranging dogs, the high isotopic similarity highlights the risk of pathogen spillover from free-ranging dogs to Darwin's foxes.

A serosurvey for spotted fever group Rickettsia and Coxiella burnetii antibodies in rural dogs and foxes, Chile.

Antibodies against Spotted Fever Group (SFG) Rickettsia and Coxiella burnetii, investigated through indirect antibody immunofluorescence tests, were detected in serum samples from 3.1% and 0% of 358 rural dogs, respectively, and in none of 32 wild foxes tested. SFG Rickettsia seropositive dogs were only detected in the Mountain Desert (8%) and the Steppe-Mediterranean (9%) regions. Exposure in the Mountain Desert, where no ticks and fleas were found on any dog, could correspond to a new SFG Rickettsia sp. recently described in soft ticks or to a related agent. Our survey confirms low endemicity in the country of C. burnetii, as observed in recent serosurveys in humans.

Assessing cross-species transmission of hemoplasmas at the wild-domestic felid interface in Chile using genetic and landscape variables analysis.

The co-occurrence of domestic cats (Felis silvestris catus) and wild felids in rural landscapes can facilitate pathogen transmission. However, in the relatively-isolated regions of southern South America there have been no comprehensive studies to assess disease transmission risks between domestic cats and forest-dwelling wild felids such as guigna (Leopardus guigna). We evaluated hemoplasma infection and the possibility of transmission between domestic cats and guignas by comparing spatial and phylogenetic patterns of pathogen prevalence. Blood/spleen samples were collected from 102 wild guignas and 262 co-occurring rural domestic cats across the entire distribution range of guigna in Chile. Hemoplasma infection was assessed by direct sequencing of the 16S RNA gene. Infection with hemoplasmas was common and geographically widespread across different bioclimatic areas for both species. The most common feline Mycoplasma species in guigna and domestic cats were Candidatus M. haemominutum (CMhm) (15.7% guigna; 10.3% domestic cat) and Mycoplasma haemofelis (Mhf) (9.8% guigna, 6.1% domestic cat). A previously undescribed Mycoplasma sp. sequence was found in two guignas and one cat. Continuous forest-landscapes were associated with higher hemoplasma-prevalence in guignas. Shared hemoplasma nucleotide sequence types between guigna and domestic cats were rare, suggesting that cross-species transmission between guignas and domestic cats may occur, but is probably uncommon. Ectoparasites, which have been linked with hemoplasma transmission, were not found on guignas and were infrequent on domestic cats. Our results suggest that transmission pathways vary among hemoplasma species and, contrary to our predictions, domestic cats did not appear to be the main driver of hemoplasma infection in guignas in these human-dominated landscapes.

The influence of Generalized Anxiety Disorder on Executive Functions in children with ADHD.

The present study was aimed at verifying whether the presence of generalized anxiety disorder (GAD) affects executive functions in children with attention-deficit hyperactivity disorder (ADHD). Two groups of children with ADHD were selected for the study according to the presence or absence of GAD. The first group of 28 children with ADHD with GAD (mean age: 9 ± 1.2; males/females: 24/4) was matched for gender, age, IQ, psychiatric comorbidity with a second group of 29 children with ADHD without GAD (mean age: 8.8 ± 0.7; males/females: 26/3). The two groups with ADHD were compared to 28 typically developing children (mean age: 8.3 ± 1.3; males/females: 23/5) on different measures involving processes especially important in inhibitory control such as rule maintenance, stimulus detection, action selection and action execution. Our results indicated that, differently from children with ADHD with GAD, only the group with ADHD without GAD showed a deficit in inhibitory control. Comorbid subgroups should be differentiated, especially, to develop specific and efficient therapeutic interventions in ADHD.

Laparoscopic or open hemicolectomy for elderly patients with right colon cancer? A retrospective analysis.

AIM: The aim of this study was to compare the short-term surgical outcomes of laparoscopically-assisted right hemicolectomy (LRH) and open right hemicolectomy (ORH) in elderly patients. Patients and methods-Results. Seventy-five patients underwent right hemicolectomy for cancer during the study period, with 41 patients aged ≥ 70 years old. Twenty-four patients underwent ORH and seventeen patients had a LRH (58% vs 42%).We found no differences between ORH and LRH in terms of mean operative time :89,5 minutes in open vs 80 minutes in laparoscopic group and return of bowel function (2,76 vs 2,54 days). Also the length of hospital stay did not differ significantly between the two groups (8,5 days in ORH vs 7 days in LRH - p 0,06). Postoperative morbidity was higher in ORH (25% vs 5%) though not statistically significant and the incidence of anastomotic leakage was similar between the two groups (8% vs 5%). CONCLUSION: Laparoscopic RH in an elderly population is feasible and safe. However, we found no evidence to suggest that it is better than open RH and think that the decision regarding the method of operation should reflect surgeon expertise, patient co-morbidities and the necessity to perform extended resections.

Multi-organ resection for locally advanced adrenocortical cancer: surgical strategy and literature review.

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with an estimated worldwide incidence of 0.5-2 per million/year. Complete surgical removal of ACC represents the current treatment of choice for this tumor. A disease-free resection margin (R0) is an important predictor of long-term survival: surgery is demanding and must be performed by a highly experienced surgical team. We report the surgical strategy adopted in a patient with locally advanced ACC and virilization to obtain a R0 resection.

Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are associated with prolongation of the QTc interval on the electrocardiogram (ECG). The QTc-interval prolongation increases the risk of life-threatening arrhythmias. However, studies evaluating the effects of TKIs on QTc intervals are limited and only consist of small patient numbers. METHODS: In this multicentre trial in four centres in the Netherlands and Italy we screened all patients who were treated with any TKI. To evaluate the effects of TKIs on the QTc interval, we investigated ECGs before and during treatment with erlotinib, gefitinib, imatinib, lapatinib, pazopanib, sorafenib, sunitinib, or vemurafenib. RESULTS: A total of 363 patients were eligible for the analyses. At baseline measurement, QTc intervals were significantly longer in females than in males (QTcfemales=404 ms vs QTcmales=399 ms, P=0.027). A statistically significant increase was observed for the individual TKIs sunitinib, vemurafenib, sorafenib, imatinib, and erlotinib, after the start of treatment (median ΔQTc ranging from +7 to +24 ms, P<0.004). The CTCAE grade for QTc intervals significantly increased after start of treatment (P=0.0003). Especially patients who are treated with vemurafenib are at increased risk of developing a QTc of ⩾470 ms, a threshold associated with an increased risk for arrhythmias. CONCLUSIONS: These observations show that most TKIs significantly increase the QTc interval. Particularly in vemurafenib-treated patients, the incidence of patients at risk for arrhythmias is increased. Therefore, especially in case of combined risk factors, ECG monitoring in patients treated with TKIs is strongly recommended.

CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia.

Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro 'patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac model of CPVT through the generation of iPSC from a CPVT patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after ß-adrenergic stimulation, resembling the cardiac phenotype of the patients. Furthermore, treatment with KN-93 (2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), an antiarrhythmic drug that inhibits Ca(2+)/calmodulin-dependent serine-threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.

Proactive and reactive control of movement are differently affected in Attention Deficit Hyperactivity Disorder children.

Attention-Deficit/Hyperactivity Disorder children are impaired in the ability to interrupt an ongoing action in relation to a sudden change in the environment (reactive control, measured by stop signal reaction time, SSRT). Less investigated is the ability to control the response when it is known in advance that it will be required to stop (proactive control, measured by change in Reaction time, RT). The study is aimed at exploring both the reactive and the proactive inhibitory control in a group of ADHD children compared to a group of age-matched controls. ADHD children (N=28) and Controls (N=28) performed 4 tasks: 2 tasks required to respond to the appearance of the go-signals (go task and nostop task) and 2 tasks to respond to the go signals in a context in which sometimes a restrain or suppression of the response was required (go-nogo task and stop task). ADHD children showed a longer SSRT compared to controls. Both groups showed an increment in RT by comparing the go-nogo to the go task and an increment in RT and SD by comparing the stop to the nostop task. ADHD children showed higher intra-individual variability (SD) compared to controls only in the stop and nostop task. ADHD children showed impaired reactive control but preserved proactive control, and the physical appearance of the go signal affected their reaction times intra-individual variability. A comparison between the reactive and proactive controls helps in defining neuropsychological profiles of ADHD children and can inspires therapeutic behavioral-cognitive strategies for response control.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

Role of first pass and delayed enhancement in assessment of segmental functional recovery after acute myocardial infarction.

PURPOSE: Assessing myocardial viability is crucial in decision making and prognostic restratification after acute myocardial infarction (MI). A number of noninvasive imaging modalities have been employed in viability identification, but contrast-enhanced magnetic resonance (MR) imaging has been shown to be extremely accurate because of its transmural resolution and precise definition of microvascular obstruction. Our purpose was to assess functional recovery after acute MI, with special focus on the role of infarct transmurality and microvascular obstruction. MATERIALS AND METHODS: Forty-six consecutive patients with first acute MI, reperfused by primary percutaneous transluminal coronary angioplasty (PTCA) (n=40) or fibrinolysis (n=6), underwent MR imaging within the first week to assess oedema, microvascular obstruction, function and viability and then again after 4-6 months to assess functional recovery and scar. RESULTS: At first MR examination, postcontrast images were analysed according to three patterns, based on a combination of first-pass and delayed-enhancement data: pattern 1 (normal first pass and late hyperenhancement <50% thickness) identified viable myocardium, whereas pattern 2 (late hyperenhancement >50% thickness, with or without first-pass perfusion defect) and pattern 3 (perfusion defect at first pass and late hypoenhancement) recognised nonviable myocardium, with 93% sensitivity, 75% specificity, 92% positive predictive value and 78% negative predictive value for identifying viable tissue. Furthermore, by dividing pattern 2 into two subpatterns, 2A and 2B, based on absence or presence of microvascular obstruction in >50% transmural infarcts, we were able to better identify the segments without recovery or that were nonviable with a 1.39 relative risk of failed recovery. CONCLUSIONS: After acute MI, not all infarcts with transmurality >50% can be considered nonviable; microvascular obstruction detected at first pass can help to better stratify these cases.

[Using parathyroid hormone 1-84 in the treatment of osteoporosis: presentation and comments of main clinical trial]. / Terapia dell'osteoporosi con paratormone 1-84: presentazione e commento dei principali trial clinici.

Osteoporosis and associated fractures associated constitute a real and serious socio-medical problem. The purpose of this research is to report the most important clinical studies regarding the effect of parathyroid hormone PTH 1-84 for osteoporosis. TOP study has demonstrated the antifracture effectiveness of PTH 1-84 in patients of primary prevention and particular attention has been paid to show a clear achievement of the primary end-point that consists in a reduction of the vertebral fracturing event. PATH study has evidenced that the administration for one year of alendronate after one year of PTH 1-84 reduced the risk of osteoporotic fractures. The primary endpoint has been the evaluation of the densitometry values in the femoral and lumbar side and the evaluation of markers of bone turnover. In this case it is possible to assume that the above mentioned therapy could offer benefits in the long term.

Heart transplantation in arrhythmogenic right ventricular dysplasia: case reports.

OBJECTIVE: Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial disease of familiar, origin where the myocardium is replaced by fibrofatty tissue predominantly in the right ventricle. Herein we have presented the clinical courses of 4 patients with ARVD who underwent orthotopic heart transplantation. PATIENTS AND METHODS: Among 358 adult patients undergoing heart transplantation, 4 (1.1%) displayed ARVD. The main indication for transplantation was the progression to heart failure associated with arrhythmias. All 4 patients displayed rapid, severe courses leading to heart failure with left ventricular involvement and uncontrolled arrhythmias. RESULTS: In all cases the transplantation was performed using a bicaval technique with prophylactic tricuspid valve annuloplasty. One patient developed hyperacute rejection and infection, leading to death on the 7th day after surgery. The other 3 cases showed a good evolution with clinical remission of the symptoms. Pathological study of the explanted hearts confirmed the presence of the disease. CONCLUSIONS: ARVD is a serious cardiomyopathy that can develop malignant arrhythmias, severe ventricular dysfunction with right ventricular predominance, and sudden cardiac death. Orthotopic heart transplantation must always be considered in advanced cases of ARVD with malignant arrhythmias or refractory congestive heart failure with or without uncontrolled arrhythmias, because it is the only way to remit the symptoms and the disease.

Evidence based medicine and effective interventions of pharmacological therapy for the prevention of osteoporotic fractures.

Osteoporosis and fractures associated with it constitute a real and serious socio-medical problem, which only recently has come to the forefront of social consciousness. The authors are carrying out a critical re-examination of the medical literature of osteoporosis pharmacological treatment. Particular attention has been paid to studies which show a clear reduction of the primary endpoint that, in the case of this pathology, consists of a reduction of the fracturing event. According to the examination of the clinical studies introduced, antiresorptive bone agents, such as alendronate and risenderonate, turn out to be molecules with higher levels of evidence implicated on the reduction of the main osteoporotic fractures, in particular the reduction of vertebral and femoral fractures. The 10 years long-term extension studies, in particular those that have seen the employment of alendronate, found a positive outcome regarding densitometry data and a favorable trend in antifracture effectiveness. Ibandronate is another amino-bisphosphonate which was recently validated as an effective drug for the treatment of osteoporosis with its documented ability to meaningfully reduce vertebral fractures. Also ranelate of strontium, a drug that seems to explain its own result in a different way from the other antiresorptive bone agents, constitutes another valid alternative in the treatment of this pathology. Both of these molecules however, need further studies in order to estimate their antifracture effectiveness in the long term, particularly those related to femoral fractures. Teriparatide and the entire molecule paratohormone are usually not prescribed for its high cost in treatment and because, typically, patients with high-risk level fractures that are already affected, produce more vertebral fractures from moderate to severe intensity.

The pathogenetic enigma of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex disease with heterogeneous clinical and anatomical features that were first described in 1721 by Antonio Vallisneri. There is still a lack of consensus regarding the criteria to be used for diagnosis of PCOS. Transvaginal ultrasonography with Doppler studies of the ovarian and pelvic vasculature plays an important role in its diagnosis, but findings must be interpreted in light of the patient's symptoms and laboratory findings.

Experimental therapy of genetic arrhythmias: disease-specific pharmacology.

The integration between molecular biology and clinical practice requires the achievement of fundamental steps to link basic science to diagnosis and management of patients. In the last decade, the study of genetic bases of human diseases has achieved several milestones, and it is now possible to apply the knowledge that stems from the identification of the genetic substrate of diseases to clinical practice. The first step along the process of linking molecular biology to clinical medicine is the identification of the genetic bases of inherited diseases. After this important goal is achieved, it becomes possible to extend research to understand the functional impairments of mutant protein(s) and to link them to clinical manifestations (genotype-phenotype correlation). In genetically heterogeneous diseases, it may be possible to identify locus-specific risk stratification and management algorithms. Finally, the most ambitious step in the study of genetic disease is to discover a novel pharmacological therapy targeted at correcting the inborn defect (locus-specific therapy) or even to "cure" the DNA abnormality by replacing the defective gene with gene therapy. At present, this curative goal has been successful only for very few diseases. In the field of inherited arrhythmogenic diseases, several genes have been discovered, and genetics is now emerging as a source of information contributing not only to a better diagnosis but also to risk stratification and management of patients. The functional characterization of mutant proteins has opened new perspectives about the possibility of performing gene-specific or mutation-specific therapy. In this chapter, we will briefly summarize the genetic bases of inherited arrhythmogenic conditions and we will point out how the information derived from molecular genetics has influenced the "optimal use of traditional therapies" and has paved the way to the development of gene-specific therapy.

Transcervical hysteroscopic myomectomy: long-term effects on abnormal uterine bleeding.

OBJECTIVE: To evaluate the effectiveness of hysteroscopic myomectomy in the treatment of symptomatic submucous leiomyomas and long-term outcomes. STUDY DESIGN: A total of 107 patients with abnormal uterine bleeding (n = 84) and/or infertility (n = 23) were submitted to hysteroscopic resection. MAIN OUTCOME MEASURES: control of menorrhagia and reproductive outcome. RESULTS: Abnormal uterine bleeding was controlled in 68 out of 84 patients with one procedure; 15 needed a second procedure for incomplete resection. Five patients had menorrhagic pathology relapse. Among 23 patients with associated infertility pregnancy was achieved in eight cases, seven went to term and one miscarried; one patient needed a second procedure. The mean follow-up was 36 months (24-60). Three patients were lost at follow-up. CONCLUSIONS: Transcervical hysteroscopic resection of submucous myomas is effective for control of abnormal uterine bleeding. Further studies are needed to define the value of such procedure in the treatment of infertility. Short and long-term results are strictly correlated to the possibility of obtaining a complete resection, which is conditioned by degree (0, 1, 2) and number of myomas.

Antiestrogenic therapy in breast cancer and endometrial modifications.

The aim of this retrospective study was to detect endometrial lesions in tamoxifen breast cancer users (menopausal state related). The meaning of genital bleeding during the treatment and the actual incidence of benign and malignant pathology of the endometrium related to length of treatment was also evaluated. Tamoxifen (TMX) is a nonsteroidal triphenylene derivate with clear antiestrogenic properties on the breast which is used as adjuvant treatment for breast cancer; potential adverse effects include endometrial lesions. Three hundred and sixty-six breast cancer patients were enrolled in this study; 292 patients were treated with 20 mg/daily of TMX as adjuvant therapy and the remaining 74 did not receive therapy. All patients were subdivided in premenopausal and postmenopausal, asymptomatic and symptomatic groups. All patients underwent ultrasound scans (to examine endometrial thickness) and hysteroscopic examinations before treatment and after one, three and five years. Endometrial biopsy under direct hysteroscopic vision was systematically performed. The pathological histology reports were classified under polyps, simple hyperplasia, complex hyperplasia, atypical hyperplasia, and carcinoma. A higher incidence of endometrial pathology was found only in symptomatic postmenopausal TMX treated patients (27.2% vs 19.5%) between the third and fifth year of treatment.

Clinical profile and genetic basis of Brugada syndrome in the Chinese population.

OBJECTIVE: To study the clinical profile and genetic basis of Brugada syndrome in Chinese patients. DESIGN: Prospective observational study. SETTING: Seven regional public hospitals, Hong Kong. MAIN OUTCOME MEASURES: The clinical and follow-up data of 50 patients (47 men, 3 women; mean age, 53 years) were collected, and genetic data of 36 probands and eight family members of three genotyped probands were analysed. RESULTS: Eight patients survived sudden cardiac death (group A), 12 had syncope of unknown origin but no sudden death (group B), and 30 were asymptomatic before recognition of Brugada syndrome (group C). Programmed electrical stimulation induced sustained ventricular arrhythmias in 88% (7/8), 82% (9/11), and 27% (3/11) of patients in group A, group B, and group C, respectively. New arrhythmic events occurred in 50% (4/8) of patients in group A and 17% (2/12) of patients in group B after a mean follow-up period of 30 (standard deviation, 13) months and 25 (7) months, respectively. All group C patients remained asymptomatic during a mean follow-up period of 25 (standard deviation, 11) months. Five of 36 probands and three of eight family members who underwent genetic testing were found to have a mutation in their SCN5A gene. CONCLUSIONS: Chinese patients with Brugada syndrome who are symptomatic have a high likelihood of arrhythmia recurrence, whereas asymptomatic patients enjoy a good short-term prognosis. The prevalence of SCN5A mutation among probands is 14%. Thus, Chinese patients with Brugada syndrome share with their western counterparts similar clinical and genetic heterogeneity.

Hormonal replacement therapy and evaluation of intrauterine pathology in postmenopausal women: a ten-year study.

BACKGROUND: To evaluate the role of hormonal replacement therapy (HRT) in determining: a) abnormal uterine bleeding (AUB); b) increased endometrial thickness at transvaginal sonography (TVS); c) the correct indication for outpatient hysteroscopy (HS) and biopsy in diagnosing intrauterine pathology. METHODS: Between April 1991 and April 2001 a group of 3,400 postmenopausal women was referred to the Department of Obstetrics and Gynecology of Rome University "La Sapienza"; 16.7% of them had received HRT. 587 out of the 3,400 women were recruited for a comparative study, including four groups. To assess statistical significance of HRT in determining AUB, and/or endometrial thickness related to malignant disease the chi-square test was used; p < 0.05 was considered significant. Histology was considered the true result (control). RESULTS: An increase in the endometrial thickness occurred significantly more often in women on HRT (p < 0.03); as well as the percentage of AUB (p < 0.0001). No difference in the incidence of endometrial adenocarcinoma was reported between the HRT and the non HRT groups. CONCLUSIONS: In postmenopausal women using HRT we can confirm that a higher incidence of signs (AUB, endometrial thickness > or = 5 mm) does not coincide with a higher incidence of malignant pathology. The data obtained from the recruited patients was arranged and evaluated by the most suitable methods for screening endometrial adenocarcinoma. According to our experience, we believe a cut-off point of 8 mm to be significant (p < 0.001) to perform an hysteroscopy and biopsy except for asymptomatic patients on HRT.