Search

Patients with chronic obstructive pulmonary disease (COPD) often suffer from other conditions, such as cardiovascular disease, that further increase the risk of adverse outcomes in this group. Serum homocysteine concentrations are positively associated with cardiovascular risk and have also been reported to be increased in COPD. This meta-analysis investigated the association between homocysteine concentrations and COPD. A systematic search of publications in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to September 2021, was conducted using the following terms: "Homocysteine" or "Hcy" and "Chronic Obstructive Pulmonary Disease" or "COPD". Weighted mean differences (WMDs) were calculated to evaluate differences in homocysteine concentrations between COPD patients and non-COPD subjects. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. Nine studies in 432 COPD patients (mean age 65 years, 65% males) and 311 controls (mean age 65 years, 56% males) were identified. Pooled results showed that serum homocysteine concentrations were significantly higher in patients with COPD (WMD = 2.91 µmol/L, 95% CI 2.00-3.82 µmol/L; p < 0.001; high certainty of evidence). No publication bias was observed. Our results support the hypothesis that increased homocysteine concentrations are significantly associated with COPD and may account, at least in part, for the increased cardiovascular risk in these patients., (© 2022. The Author(s).)

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by a state of persistent inflammation and oxidative stress. The presence of oxidative stress in COPD is the result of an imbalance between pro-oxidant and antioxidant mechanisms. The aim of this review was to investigate a possible association between glutathione peroxidase (GPx), a key component of antioxidant defense mechanisms, and COPD. A systematic search for relevant studies was conducted in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to June 2021. Standardized mean differences (SMDs) were used to express the differences in GPx concentrations between COPD patients and non-COPD subjects. Twenty-four studies were identified. In 15 studies assessing whole blood/erythrocytes (GPx isoform 1), the pooled results showed that GPx concentrations were significantly lower in patients with COPD (SMD = -1.91, 95% CI -2.55 to -1.28, p < 0.001; moderate certainty of evidence). By contrast, in 10 studies assessing serum/plasma (GPx isoform 3), the pooled results showed that GPx concentrations were not significantly different between the two groups (very low certainty of evidence). The concentration of GPx-1, but not GPx-3, is significantly lower in COPD patients, suggesting an impairment of antioxidant defense mechanisms in this group.

Oxidative stress induced by nocturnal intermittent hypoxia plays a significant pathophysiological role in obstructive sleep apnea (OSA). Malondialdehyde (MDA), one of the most commonly investigated markers of lipid peroxidation, might assist with the monitoring of oxidative balance in OSA. We conducted a systematic review and meta-analysis to evaluate the differences in circulating MDA concentrations between patients with OSA and non-OSA controls. A systematic search was conducted in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to December 2020 by using the following terms: "malondialdehyde" or "MDA"; and "Obstructive Sleep Apnea Syndrome", "OSAS" or "OSA". We identified 26 studies in 1223 OSA patients and 716 controls. The pooled MDA concentrations were significantly higher in patients with OSA (standardized mean difference (SMD) 1.43 μmol/L, 95% confidence interval (CI) 1.03 to 1.83 μmol/L, p < 0.001). There was extreme heterogeneity between the studies (I 2 = 92.3%, p < 0.001). In meta-regression analysis, the SMD was significantly associated with age, the assay type used and publication year. In our meta-analysis, MDA concentrations were significantly higher in OSA patients than in controls. This finding suggests that MDA, which is a marker of lipid peroxidation, is involved in the pathogenesis of OSA and provides insights for future studies investigating its potential clinical use.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease characterized by a not fully reversible airflow limitation associated with an abnormal inflammatory response. Exacerbations of COPD are of major importance in the acceleration of disease progression, in healthcare costs, and negatively affect the patient's quality of life. Exacerbations are characterized by a further increase in the airway inflammation likely driven by oxidative stress. In order to deepen the knowledge about this topic, several studies have focused on oxidative stress biomarkers levels. This review summarizes the literature findings about oxidative stress biomarkers in exacerbated COPD patients compared to ones in the stable state., Methods: a systematic search in electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to January 2021, was conducted using the terms: "oxidative stress", "chronic obstructive pulmonary disease" or "COPD", "exacerbation"., Results: 23 studies were selected for the systematic review. They showed the presence of an imbalance between oxidant and antioxidant molecules in favor of the former in exacerbation of COPD., Conclusions: future studies using standardized methods in better characterized population are needed. However, this review suggests that targeting oxidative stress could be useful in monitoring the disease progression in COPD patients and especially in those more susceptible to exacerbations.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that may have a negative impact on both patients' quality of life and survival. Patients with COPD frequently suffer from heart failure (HF), likely owing to several shared risk factors., Aim: To evaluate the differences in treatment of COPD with and without HF comorbidity according to COPD severity in the general practitioner setting., Methods: We conducted an observational, retrospective study using data obtained from the Italian Health Search Database, which collects information generated by the routine activity of general practitioners. The study sample included 225 patients with COPD, alone or combined with HF., Findings: It has been found that the prevalence of some comorbidities such as diabetes and HF significantly increases with the severity of COPD. Regarding pharmacological treatment, a reduction in the prescription of individually administered long-acting β 2-agonists (LABAs) and long-acting anticholinergics (LAMAs) has been observed with increasing severity of the disease. Moreover, an increase in the prescription of both the combination of the two bronchodilators (LABA + LAMA) and their association with inhaled corticosteroids has been observed with increasing severity of COPD. The prescription of β-blockers in patients with COPD suffering from HF comorbidity decreases from 100% in stage I to less than 50% in the other stages of COPD. This study shows that general practitioners do not follow the guidelines recommendations for the management of patients with COPD in the different stages of the disease, with and without HF comorbidity, as well as in the management of HF. Further efforts must be made to ensure adequate treatment for these patients.

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airflow limitation that is not fully reversible after inhaled bronchodilator use associated with an abnormal inflammatory condition. The biggest risk factor for COPD is cigarette smoking. The exposure to noxious chemicals contained within tobacco smoke is known to cause airway epithelial injury through oxidative stress, which in turn has the ability to elicit an inflammatory response. In fact, the disruption of the delicate balance between oxidant and antioxidant defenses leads to an oxidative burden that has long been held responsible to play a pivotal role in the pathogenesis of COPD. There are currently several biomarkers of oxidative stress in COPD that have been evaluated in a variety of biological samples. The aim of this review is to identify the best studied molecules by summarizing the key literature findings, thus shedding some light on the subject., Methods: We searched for relevant case-control studies examining oxidative stress biomarkers in stable COPD, taking into account the analytical method of detection as an influence factor., Results: Many oxidative stress biomarkers have been evaluated in several biological matrices, mostly in the blood. Some of them consistently differ between the cases and controls even when allowing different analytical methods of detection., Conclusions: The present review provides an overview of the oxidative stress biomarkers that have been evaluated in patients with COPD, bringing focus on those molecules whose reliability has been confirmed by the use of different analytical methods., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Elisabetta Zinellu et al.)

Background: It is amply reported that patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular disease (CVD). Recent evidence suggests that COPD patients have elevated concentrations of plasma homocysteine (Hcy), a transsulfuration pathway analyte that is commonly regarded as a CVD risk factor., Design: We comprehensively investigated the plasma concentrations of transsulfuration pathway analytes, and their relationship with markers of oxidative stress and inflammation, to identify which low molecular thiols might play a pathophysiological role both in CVD and in COPD. Hcy, cysteine (Cys), glutathione (GSH), cysteinylglycine (CysGly), glutamylcysteine (GluCys), taurine (Tau), oxidative stress markers (TBARS and protein-SH, PSH) and the inflammation marker kynurenine/tryptophan (Kyn/Trp) ratio were measured in 54 COPD patients and 54 control subjects., Results: We found increased concentrations of total Hcy (P < .01) and total CysGly (P < .05) in COPD patients when compared to controls. Total Hcy and CysGly were also significantly associated with abnormal lung function parameters and COPD severity. In COPD patients, total Hcy was significantly associated with the Kyn/Trp ratio (P = .0017) whereas total CysGly was significantly associated with both PSH (P = .0298) and the Kyn/Trp ratio (P = <.0001)., Conclusion: Both total Hcy and CysGly concentrations were significantly associated with the presence and severity of COPD and with markers of oxidative stress (total CysGly) and inflammation (total Hcy and CysGly). This suggests that specific low molecular mass thiols might play a role in the inflammatory and oxidative stress pathways involved in both CVD and COPD., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: The identification of neck lymph node (LN) metastases represents a very important issue in the management of patients with differentiated thyroid carcinoma (DTC). To this purpose, in the present study, we used 131I-SPECT/CT as a diagnostic imaging procedure., Methods: A consecutive series of 224 DTC patients with ascertained neck radioiodine-avid foci at 131 I-SPECT/CT during long-term follow-up was evaluated. All patients had already undergone total thyroidectomy and radioiodine therapy and had been classified as follows: 62 at high risk (H), 64 at low risk (L) and 98 at very low risk (VL). 131 I-Whole body scan (WBS) followed by SPECT/CT was performed in all cases., Results: In the 224 patients, 449 neck iodine avid foci were ascertained at SPECT/CT, while 322 were evidenced at WBS in 165/224 patients. WBS classified as residues 263/322 foci and as unclear 59/322 foci; among the former foci SPECT/CT correctly characterized 8 LN metastases and 3 physiologic uptakes and among the latter, it pinpointed 26 LN metastases, 18 residues, and 15 physiologic uptakes. SPECT/CT also classified 127 foci occult at WBS as 59 LN metastases and 68 residues. Globally, SPECT/CT identified 93 LN metastases in 59 patients (26 H, 20 L, 13 VL), while WBS evidenced 34 in 25 cases. All 13 VL patients, T1aN0M0, 5 of whom with LN near sub-mandibular glands, had thyroglobulin undetectable or < 2.5 ng/ml. Globally, SPECT/CT obtained an incremental value than WBS in 45.5% of patients, a more correct patient classification changing therapeutic approach in 30.3% of cases and identified WBS false-positive findings in 8% of cases., Conclusions: 131 I-SPECT/CT proved to correctly detect and characterize neck LN metastases in DTC patients in long-term follow-up, improving the performance of planar WBS. SPECT/CT routine use is thus suggested; its role is particularly relevant in patients with WBS inconclusive, VL, T1aN0M0 and with undetectable or very low thyroglobulin levels.

Introduction : Endometrial cancer (EC) is one of the most frequent gynecological cancers worldwide. The gold standard treatment of EC is most certainly surgery and may very well be the only therapy in the early stages of disease. To improve outcomes in non-early EC, adjuvant therapy is often employed but this is not standardized. Adjuvant options can include radiotherapy, chemotherapy or a combination of both. Adjuvant chemotherapy could be indicated in high-risk stage I and II or advanced stage EC. Several clinical trials are ongoing in an attempt to define the optimal adjuvant treatment. Furthermore, chemotherapy is the front-line therapy in advanced unresectable, metastatic or recurrent endometrial cancer. Areas covered : Herein, the authors review the first-line chemotherapy for the treatment of endometrial cancer and provide their expert perspectives on these therapies. Expert opinion : Chemotherapy is fundamental in advanced/recurrent EC. Further evidence is needed to characterize the role of adjuvant chemotherapy. Future studies should consider genomic and molecular heterogeneities to identify even more efficient tailored therapies.

This observational study was conducted in premenopausal women who presented themselves at the Obstetrics and Gynecology Department of the University Hospital of Cagliari (Italy), for heavy menstrual bleeding (HMB) dependent on uterine myomas. After a screening visit, 19 women without contraindications to ulipristal acetate (UPA) treatment, were included in the study that envisaged 12 months of observation in which each subject was asked to assume UPA (tablet of 5 mg, ESMYA ® , one tablet a day for 3 months: first cycle) two menstrual cycles of interruption and a second ESMYA ® cycle, followed by 3 months of observation (third follow-up month, visit 4). The significant decrease of myoma volume, diagnosed after the first ESMYA ® cycle, persisted until the visit 4. The HMB significantly decreased during the ESMYA ® treatment and persisted until visit 4. The quality of life (QoL), evaluated with the questionnaire SF-36, significantly improved during the study. The values of estradiol (E2), biochemical parameters of bone metabolism, as well as those of lumbar and hip bone mineral density, did not change during the study in comparison with basal levels. The efficacy of two repeated ESMYA ® cycles to treat uterine myomas and their related symptoms improves the QoL without interfering with bone health.

Small airways were historically considered to be almost irrelevant in the development and control of pulmonary chronic diseases but, as a matter of fact, in the past few years we have learned that they are not so "silent". Asthma is still a worldwide health issue due to the great share of patients being far from optimal management. Several studies have shown that the deeper lung inflammation plays a critical role in asthma pathogenesis, mostly in these not well-controlled subjects. Therefore, assessing the degree of small airways inflammation and impairment appears to be a pivotal step in the asthmatic patient's management. It is now possible to evaluate them through direct and indirect measurements, even if some obstacles still affect their clinical application. The success of any treatment obviously depends on several factors but reaching the deeper lung has become a priority and, for inhaled drugs, this is strictly connected to the molecule's size. The aim of the present review is to summarize the recent evidence concerning the small airway involvement in asthma, its physiopathological characteristics and how it can be evaluated in order to undertake a personalized pharmacological treatment and achieve a better disease control.

Papillary thyroid microcarcinoma (PTMC) usually has a favorable prognosis but can also be aggressive, with neck and distant metastases. We evaluated the diagnostic role of 131 I SPECT/CT in detecting metastases in PTMC patients during long-term follow-up and whether the procedure should be included in the current diagnostic protocol. Methods: We retrospectively studied 351 consecutive PTMC patients who had undergone thyroidectomy and radioiodine therapy; 21 were at high risk, 94 at low risk, and 236 at very low risk. During follow-up, the patients underwent diagnostic 131 I whole-body scanning (WBS) followed by SPECT/CT. Results: WBS found 248 radioiodine-avid foci in 126 patients, and SPECT/CT found 298 in 139 patients, confirming all foci found on WBS. SPECT/CT also correctly classified 76 of the avid foci as unclear or wrongly classified on WBS. Globally, SPECT/CT detected and correctly classified 64 neoplastic lesions in 27 of 30 patients with metastases, and WBS evidenced 39 of 64 lesions, 28 of which were unclear or wrongly classified, in 16 of the 30 patients. Nineteen of 27 patients, including 13 at very low risk, had only neck metastases, 9 of 19 being T1aN0M0 with an undetectable thyroglobulin level. Three of 27 patients, including 1 at very low risk, had only distant metastases with an undetectable or very low thyroglobulin level. Five of 27 patients had neck and distant metastases with a thyroglobulin level <2.5 ng/mL in 1 case, between 2.5 and 10 in 3 cases, and >10 in the remaining case. SPECT/CT also reduced WBS false-positive results in 15 of 139 patients (10.8%). SPECT/CT had an incremental value over WBS in 38.1% of patients with positive findings and changed the classification and therapeutic management in 21.6%. Conclusion: Metastases occurred in 8.5% of patients during long-term follow-up. SPECT/CT performed better than WBS, particularly in patients at very low risk with inconclusive WBS results, a TNM stage of T1aN0M0, and an undetectable or very low level of thyroglobulin. Prolonged surveillance is justified in PTMC patients, and wider use of 131 I SPECT/CT in the diagnostic protocol is suggested., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

The vaginal immune system (VIS) is the first defense against antigens recognized as foreign. Substances capable of locally activating the VIS could be a valid strategy to treat vulvo-vaginal infections (VVI), caused by changes in the vaginal ecosystem, such as bacterial vaginosis (BV), vulvo-vaginal candidiasis (CA), and mixed vaginitis (MV). Bacterial lysates, obtained by crushing bacterial cultures, exert immuno-modulatory activities. The parietal fraction from Propionibacterium acnes is a patent of Depofarma (MoglianoVeneto, Italy). The preparation that associates such fraction to hyaluronic acid and polycarbophil is a registered trademark, commercially available in Italy as vaginal gel, Immunovag ® . The study aimed to evaluate whether a 5-day-treatment with Immunovag ® improves the symptoms and signs of VVI, in 60 women with Gardnerella vaginalis (GV), 154 with CA, 95 with MV, diagnosed with vulvar vaginal swab (VVS), and in 283 with BV, diagnosed with the Amsel criteria. At the end of the treatment (visit 2), the symptoms and signs of VVI disappeared in a significant number of subjects (χ 2 p < .02 vs pre-treatment) in all VVI groups, and their intensity was significantly (p < .0002) reduced in the subjects in which they were still present. Immunovag ® represents a valid treatment of VVI induced by changes in the vaginal ecosystem.

Objectives: To evaluate the diagnostic accuracy of 2-dimensional (2D) and 3-dimensional (3D) transvaginal ultrasonography (US) in comparison with magnetic resonance imaging (MRI) for identification of deep infiltrating endometriosis., Methods: In this prospective observational study, 159 premenopausal women who underwent surgery for a clinical suspicion of deep infiltrating endometriosis were prospectively enrolled. All women underwent 2DUS, 3DUS, and MRI. The following 3 locations of deep endometriosis were considered: (1) intestinal; (2) other posterior lesions (retrocervical septum, rectovaginal septum, uterosacral ligaments, and vaginal fornix); and (3) anterior. The sensitivity, specificity, positive predictive value, and negative predictive value of 2D and 3D transvaginal US in comparison with MRI were determined., Results: Intestinal deep infiltrating endometriosis was identified by 2DUS in 56 of 66 patients, by 3DUS in 59 of 66, and by MRI in 61 of 66. A receiver operating characteristic curve analysis showed optimal results for 2DUS, 3DUS, and MRI (areas under the curve, 0.86, 0.915, and 0.935, respectively) with a statistically significant difference between 2DUS and MRI (P = .0103), even when the 95% confidence interval showed an overlap. Other posterior deep infiltrating endometriosis was identified by 2DUS in 55 of 75 patients, by 3DUS in 65 of 75, and by MRI in 66 of 75. A receiver operating characteristic curve analysis showed very good results for 2DUS, 3DUS, and MRI (areas under the curve, 0.801, 0.838, and 0.857) with no statistically significant differences. In the 12 women with deep infiltrating endometriosis in the anterior location, the nodules were correctly identified by 2DUS in 3 of 12 patients, by 3DUS in 5 of 12, and by MRI in 6 of 12., Conclusions: Our results seem to suggest that there is a statistically significant difference between 2DUS and MRI for the intestinal location of deep infiltrating endometriosis, whereas no differences were found among the techniques for the other locations., (© 2017 by the American Institute of Ultrasound in Medicine.)

This observational study was conducted in healthy premenopausal women, who presented themselves for contraception with an intrauterine system (IUS) releasing LNG (6 mcg/d) (Jaydess®, Bayer, Germany) at the outpatient Family Planning Clinics of the Departments of Obstetrics and Gynaecology of the Universities of Cagliari and Sassari (CA/SS), University-Hospitals of CA/SS (Italy). After a screening visit, 31 women without contraindications to Jaydess® were included in the study. No difficulty in Jaydess® insertion (Ji) was found in 87% of subjects, with pelvic pain (PP) (visual analogic scale, VAS:5.33 ± 2.54) reported by 27/31 subjects at the Ji. Pelvic pain was reported by 17/31 subjects on the first day (VAS: 3.07 ± 3.1), 16/31 subjects on the second day (VAS:2.37 ± 2.71), and 11/31 subjects on the third day (VAS:1.18 ± 2.02) from Ji, with a significant (p < .001) decrease in the intensity. The primary purposes of the study were to evaluate whether a 12-month-treatment (12-M-T) with Jaydess® interferes on either the quality of life (QoL) or sexuality. Jaydess® did not modify either QoL or sexuality in the 25 subjects who completed the 12-M-T. Throughout the 12-M-T, PP, or pregnancies were not found; the menstrual blood loss was significantly (p < .0001) reduced, and the intensity VAS of dysmenorrhea (#14 subjects) significantly (p < .001) improved.

Introduction: The medical strategy to antagonize myoma size and related-symptoms is to reduce estrogen and progesterone activity on myomas. This can be obtained with the GnRH agonist (GnRHa) or with compounds that antagonize progesterone stimulatory activity on myomas. Selective progesterone receptor modulators (SPRMs) bind progesterone receptor (PR), leading to both agonist and antagonist effects. The result of SPRMs's action is tissue-specific and it depends on the particular affinity and strength of each SPRM. Area covered: Ulipristal acetate (UPA) is the first SPRM registered for myoma treatment. UPA reduces heavy uterine bleeding within 7 days from the onset of treatment, whereas a longer time is required with GnRHa treatment. Vilaprisan is a novel powerful SPRM. Phase I and II studies give encouraging results on the efficacy of vilaprisan at different doses. Like other SPRMs, vilaprisan induces benign changes of endometrium (PR modulator-associated endometrial changes, PAECs). These disappear as treatment is discontinued. Unlike GnRHa treatment, neither UPA nor vilaprisan induce hypoestrogenism and associated symptoms. Phase III studies are ongoing to confirm efficacy and safety of vilaprisan in long-term treatment of symptomatic fibroids. Expert opinion: It is fundamental to underline the rapidity of action (only 3 days) in the control of myoma-related bleeding.

This observational study was conducted in healthy premenopausal women, who presented themselves for contraceptive advice at the outpatient Family Planning Clinics of the Department of Obstetrics and Gynecology of the University of Cagliari, Hospital-University of Cagliari (Italy). After a screening period of three menstrual cycles, 48 women without contraindications to estroprogestin contraceptives (OCs) were included in the study. The primary purposes of the study were to evaluate whether a 12-month-treatment with the combined OC containing micronized estradiol (1.5 mg, E2) plus nomegestrol acetate (2.5 mg, NOMAC) (E2/NOMAC) interfere on anthropometric indices (AI), body composition (BC) and psychological status (PS). In subjects with dysmenorrhea (#36), its intensity was evaluated using the visuo analogic scale (VAS), both before and during the 12-month-treatment with E2/NOMAC. E2/NOMAC did not modify neither AI nor BC in the 40 subjects who concluded the study. The PS and the VAS of dysmenorrhea were significantly (p < 0.0001) improved from the first cycle of treatment and throughout the E2/NOMAC treatment in comparison with basal values. The study suggests that E2/NOMAC is devoid of negative effects on AI and BC, with additional benefits on PS and dysmenorrhea.

In a retrospective study performed in non-functioning GEP tumor patients we further investigated 111 In-Pentetreotide SPECT/CT usefulness in diagnosis, staging and follow-up also evaluating whether the procedure may give more information than conventional imaging procedures (CIP), such as CT, MRI, US. We enrolled 104 consecutive patients with non-functioning GEP tumors, 30 in initial diagnosis and staging phases (IDS) and 74 in follow-up (FU). All patients underwent somatostatin receptor scintigraphy (SRS) whole body scan at 4, 24 and, if necessary, 48 hours followed by abdominal and chest SPECT/CT after 111 In-Pentetreotide 148-222 MBq i.v. injection. The patients previously underwent 2 to 3 CIP. At both CIP and SPECT/CT, 34/104 patients were classified as no evidence of disease (NED); in 70/104 patients, neoplastic lesions were ascertained and 12 IDS and 17 FU were classified as not operable and treated with octeotride or chemotherapy. SPECT/CT and CIP were concordantly positive in 44 patients, while only CIP was positive in 6 cases and only SPECT/CT in 20. Both per-patient sensitivity and accuracy of SPECT/CT (91.4 and 94.2%, respectively) were higher than CIP (71.4 and 80.8%, respectively), but not significantly. Globally, 292 lesions were ascertained: 141 hepatic, 78 abdominal extra-hepatic and 73 extra-abdominal. CIP detected 191/292 (65.4%) lesions in 50 patients, while SPECT/CT 244/292 (83.6%) in 64, the difference being significant (p<0.0001). No false positive results were found at both SPECT/CT and CIP. Both SPECT/CT sensitivity and accuracy were higher than CIP in G1, G2, neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC) patients, but significantly only for G1. Globally, SPECT/CT incremental value than CIP was 35.6%. SPECT/CT correctly modified CIP classification and patient management in 27.9% of cases, while it down-staged the disease than CIP in 9.6% of cases. However, the two procedures combined use could achieve the highest accuracy value. 111 In-Pentetreotide SRS, acquired as SPECT/CT, showing high sensitivity and accuracy values, more elevated than CIP in the present study, can still have a wide employment in the routine diagnostic protocol of non-functioning GEP tumors with significant impact on patient management and therapy planning. The procedure is simple to perform, has limited cost and wide availability in all Nuclear Medicine Centers., Competing Interests: None.

Introduction: Suppression of sex-steroid secretion is required in a variety of gynecological conditions. This can be achieved using gonadotropin releasing hormone (GnRH) agonists that bind pituitary gonadotropin receptors and antagonize the link-receptor of endogenous GnRH, inhibiting the mechanism of GnRH pulsatility. On the other hand, GnRH antagonists immediately reduce gonadal steroid levels, avoiding the initial stimulatory phase of the agonists. Potential benefits of GnRH antagonists over GnRH agonists include a rapid onset and reversibility of action. Older GnRH antagonists are synthetic peptides, obtained by modifications of certain amino acids in the native GnRH sequence. They require subcutaneous injections, implantation of long-acting depots. The peptide structure is responsible for histamine-related adverse events and the tendency to elicit hypersensitivity reactions., Areas Covered: Research has worked towards the development of non-peptidic molecules exerting antagonist action on GnRH. They are available for oral administration and may have a more beneficial safety profile in comparison with peptide GnRH antagonists. This article focuses on the data of the literature about elagolix, a novel non-peptidic GnRHantagonist, in the treatment of endometriosis., Expert Opinion: Elagolix demonstrated efficacy in the management of endometriosis-associated pain and had an acceptable safety and tolerability profile. However, further studies are necessary to evaluate its non-inferiority in comparison with other endometriosis's treatments.

Background: The forced expiratory volume at first second (FEV(1)) during spirometry reflects the severity of chronic obstructive pulmonary disease (COPD) and is known to be an important prognostic factor. It is uncertain whether the response to short-acting bronchodilators may predict long-term outcomes such as hospitalizations and mortality., Methods: We retrospectively studied a total of 1203 consecutive COPD patients without significant comorbidities during a mean (±SD) of 69 ± 39 months of follow-up. At baseline the subjects were classified as those with positive or negative bronchodilator test (BDT) and also in quartiles of absolute bronchodilator response to 400 μg of salbutamol. Hospital visits and mortality were the end points., Results: A positive bronchodilator test was observed in 332 (27.6%) of the patients. There were 73 (21.9%) deaths in patients with a positive BDT versus 253 (28.7%) in those with a negative BDT (p = 0.04). In adjusted Cox regression analysis a positive BDT was significantly associated with a prolonged time to first hospitalization. After stratifying the population by quartiles of response to BDT, a dose-response relationship was observed with the best outcomes in the quartile with highest level of airflow reversibility, even after controlling for age, sex, BMI, smoking status and baseline postbronchodilator FEV(1)., Conclusions: In a large population of well characterized COPD patients without significant comorbidities, those demonstrating higher levels of reversibility at baseline presented better long-term outcomes even after controlling for other known prognostic factors., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We investigated whether a formulation containing vitamins and minerals (vit&min) could improve the worsening of mood changes occurring after delivery ("a.d."). The study was performed in 552 healthy non-anaemic puerperal women ("p.w") without risk factors for puerperal depression ("p.d"). They were at their first full-term pregnancy, and spontaneously delivered healthy newborns. The Edinburgh Depression Postnatal scale (EPDS) evaluates the psychological status of "p.w". EPDS was administered the 3rd (visit 1), 15th (visit 2) and 30th (visit 3) day "a.d.". An EPDS >12 indicates a major susceptibility to "p.d". At the same time intervals, haemoglobin, iron and ferritin (haematological parameters) levels were evaluated. After visit 1, the subjects were randomized to vit&min treatment (group A; N.274) or to calcium/vitamin D3 treatment (group B; N.278). In both groups haematological parameters significantly increased without differences between the groups. EPDS score improved in both groups, but in the group A, the EPDS decrease was significantly larger (p < 0.05) in comparison to the group B. This effect is mainly evident in subjects with a basal EPDS ≥ 12. An early examination of psychological condition could select "p.w." with a high susceptibility to neuronal changes occurring postpartum. Vit&min favourably modulates brain functions antagonizing the evolution to "p.d".

With the aim of providing better clinical characterisation of patients with α1-antitrypsin deficiency (AATD), we analysed the data of adult patients with severe AATD enrolled in the Spanish and Italian national registries. We assessed 745 subjects, 416 of whom were enrolled in the Spanish registry and 329 in the Italian registry. 57.2% were male and 64.9% were smokers or former smokers with a mean±sd age of 49.9±13.8 years. Most (81.2%) were index cases, mainly having the PI*ZZ genotype (73.4%), and the mean±sd diagnostic delay was 9.0±12.1 years. Patients with chronic bronchitis were younger, had better preserved lung function and lower tobacco consumption. Overlap patients (chronic obstructive pulmonary disease with asthma) were mainly females, more frequently never-smokers and received respiratory medications more often. 48% of emphysema, 27.5% of chronic bronchitis and 44.8% of overlap subjects were receiving augmentation therapy. Compared with PI*ZZ patients (n=547), the PI*SZ (n=124) subjects were older at diagnosis and had more preserved lung function, despite a higher mean smoking consumption. Early diagnosis of AATD is still an unmet need. Augmentation therapy is administered to similar proportions of patients with different clinical phenotypes. PI*ZZ patients in both registries had more severe respiratory disease than those with PI*SZ, despite lower smoking levels.

Introduction: Progesterone (P), and its receptors (PRs), play a key role in uterine leiomyoma growth. Selective progesterone receptor modulators exert mixed antagonist and agonist effects on the PRs. Mifepristone, a PR-antagonist, reduces leiomyoma volume and related symptoms. Ulipristal acetate (UPA) exerts a potent antiprogestin activity, with less antiglucocorticoid activity compared to mifepristone. This property provides potential advantages for long-term use., Areas Covered: This paper focuses on the effect of UPA on leiomyoma's growth and related symptoms in women. The authors also evaluate UPA's efficacy in reducing leiomyoma's size and menorrhagia in Phase II/III trials., Expert Opinion: In the authors' opinion, UPA (5 mg/day) over 3 months can be used to plan the surgery in women with symptomatic leiomyomas. The tolerability and the safety of treatment over a period longer than 3 months have to be evaluated. The results of the follow-up treatment suggest that further studies could successfully evaluate the efficacy and the tolerability of intermittent 3-month courses of treatment.

The diagnosis rate of deep pelvic endometriosis is increasing. Endometrial stromal sarcoma (ESS) is a rare neoplasm. Extragenital ESS is an extremely uncommon event. Very few cases of extragenital ESS have been reported to date. The diagnosis of this entity is very difficult in some instances. Knowledge about its management is also limited. In this paper, we review the current literature on the clinical management, histology, immunohistochemistry, treatment and outcome of ESS arising in pelvic endometriosis., (Copyright © 2012 S. Karger AG, Basel.)

Endometrial cancer is the most common malignancy of the female genital tract in developed countries. The primary treatment for women with endometrial cancer is surgical, as well as the staging of the pathological spread pattern of this carcinoma outside of the uterus. A complete surgical staging should include both pelvic and para-aortic lymphadenectomy. The vast majority of endometrial cancers are diagnosed at a very early stage owing to the early presentation as abnormal uterine bleeding. In women with early-stage endometrial cancer the systematic pelvic and para-aortic lymphadenectomy may produce additional morbidity without the benefit of appropriate surgical staging. The procedure of sentinel lymph node (SLN) biopsy after lymphatic mapping has been introduced for patients with cancers of various organs in an effort to avoid complete systematic lymphadenectomy whenever possible. In the case of gynecological malignancies, the reliability of the SLN detection procedure has been extensively investigated in vulvar and cervical cancer. This article focuses on the peculiar aspects of intraoperative lymphatic mapping techniques and SLN procedures in endometrial cancer.

Study Objective: To evaluate the specificity of blind biopsy in detecting benign intracavitary lesions as causes of postmenopausal bleeding in comparison with directed biopsy via hysteroscopy., Design: Prospective trial without randomization (Canadian Task Force classification II-1)., Setting: University hospital., Patients: Three hundred nineteen postmenopausal women with abnormal uterine bleeding., Interventions: All patients underwent both blind biopsy (Novak's curette) and directed biopsy via hysteroscopy (after at least a week). All patients with benign intracavitary lesions underwent operative hysteroscopy to enable the removal of polyps and intracavitary myomas or endometrial resection if required. All patients with pathologic reports of complex hyperplasia and atypical hyperplasia (20 patients) underwent vaginal hysterectomy with bilateral adnexectomy. All patients with histology reports of endometrial carcinoma (15 patients) underwent abdominal hysterectomy, bilateral adnexectomy, and pelvic lymphadenectomy. Histopathologic findings from endometrial specimens obtained after operative hysteroscopy or uterine specimens obtained after hysterectomy were used as a reference test to establish the prevalence of disease., Measurements and Main Results: The sensitivity, specificity, accuracy, and positive and negative predictive values of blind biopsy and hysteroscopy were assessed to distinguish benign intracavitary formations such as polyps, submucous myomas, and endometrial hyperplasia in postmenopausal patients with abnormal uterine bleeding. The level of agreement was evaluated by use of the coefficient of concordance kappa. Blind biopsy showed a sensitivity of 11% and a specificity of 93%, with an accuracy of 59% in detecting endometrial polyps, a sensitivity and specificity of 13% and 100%, respectively, with an accuracy of 98% for submucous myomas, and values of 25%, 92%, and 80%, respectively, in diagnosing hyperplasia. On the other hand, hysteroscopy demonstrated a sensitivity of 100% and a specificity of 97%, with an accuracy of 91% in diagnosing endometrial polyps, a sensitivity and specificity of 100% and 98%, respectively, with an accuracy of 99% for submucous myomas. The coefficient of concordance kappa (95% CI) was 0.12 for blind biopsy and 0.82 for hysteroscopy, corresponding, respectively, to slight concordance and almost perfect agreement with final pathologic diagnosis., Conclusions: Blind biopsy (Novak's curette) demonstrates very low sensitivity and accuracy in the diagnosis of benign focal intracavitary lesions. Hysteroscopy is confirmed as the gold standard in the assessment of abnormal uterine bleeding in menopause, permitting the elimination of the false-negative results of blind biopsy through direct visualization of the uterine cavity and the performance of targeted biopsy in case of doubt.

Objective: To determine the accuracy of transvaginal ultrasonography (TVUS) using a modified "tenderness-guided" approach in the diagnosis of deep endometriosis of the cul-de-sac, retrocervical region, and rectovaginal septum., Design: Prospective study., Setting: Academic department of obstetrics and gynecology., Patient(s): Fifty women scheduled for laparoscopy for chronic pelvic pain., Intervention(s): All patients underwent TVUS. The modified tenderness-guided approach consisted of TVUS combined with the introduction of 12 mL of ultrasound transmission gel (instead of the usual 4 mL) in the probe cover to create a stand-off to visualize the near-field area. The posterior fornix was evaluated accurately with an up-and-down sliding movement of the probe. In addition, when the patient indicated that tenderness was evoked by the probe's pressure, the sliding movement was stopped, and particular attention was paid to the painful site for detection of endometriosis lesions., Main Outcome Measure(s): Sensitivity, specificity, and kappa values., Result(s): Using this approach, we obtained a specificity of 95% with a sensitivity of 90%, associated with a very high kappa value of 0.86 (95% CI, 0.56-0.91)., Conclusion(s): Our new TVUS approach appears to be an accurate, inexpensive, and less invasive method for the diagnosis of deep endometriosis.

Objective: To assess whether IV tramadol before outpatient hysteroscopy could reduce procedure-related pain., Design: A randomized double-blind placebo controlled trial., Setting: Outpatient Hysteroscopy Centre in the Department of Obstetrics and Gynaecology of Cagliari University., Patient(s): Fifty healthy, parous, women who underwent outpatient diagnostic hysteroscopy and endometrial biopsy., Intervention(s): Random IV infusion of tramadol or placebo before hysteroscopy and endometrial biopsy were performed., Main Outcome Measure(s): Visual analogue scale of pain was measured both immediately after and 15 minutes after the procedure. Stress hormones (ACTH, cortisol), blood pressure, and heart frequency were evaluated before, during, and 15 minutes after the procedure., Result(s): In the tramadol group, the visual analogue scale of pain was significantly lower than in the placebo group both immediately after the procedure and 15 minutes later. Basal levels of ACTH and cortisol did not differ between the groups. In both groups, the ACTH levels remained unchanged during the study, and the cortisol levels were higher 15 minutes after the procedure than before the procedure. Procedure time, heart frequency, blood pressure, and adverse effects did not differ between the groups., Conclusion(s): In parous women without uterine malformations, a treatment with tramadol before hysteroscopy and endometrial biopsy appears to be capable of reducing the pain and discomfort that are associated with this procedure.

Objective: This study was undertaken to identify whether ultrasonography with color Doppler can identify and triage the patients with adnexal masses to the most appropriate surgical approach., Study Design: Four hundred fifty-three pelvic masses were included in the study and underwent ultrasonography before surgical treatment for adnexal masses. Masses that showed a typical benign pattern at B-mode ultrasonography (very low risk of malignancy) were treated by conventional laparoscopy without further evaluation. Masses that extended above the umbilicus were consider at very high risk and treated by laparotomy. All other adnexal masses were evaluated with power Doppler. Masses with central vascularization (high risk of malignancy) were submitted to laparotomy or laparoscopy with additional tools, whereas masses with peripheral or absent flow (low risk of malignancy) were submitted to conventional laparoscopy., Results: Among 284 very low-risk, 32 low-risk, 46 high-risk, 91 very high-risk masses, the rate of malignant masses were 0%, 0%, 52%, and 78%, respectively. The use of color Doppler increases the diagnostic accuracy of B-mode ultrasonography in the diagnosis of adnexal malignancies because of a significantly higher specificity (0.91 vs 0.82, P < .001)., Conclusion: The evaluation of vessel distribution by color Doppler seems a safe diagnostic procedure, permitting to treat by laparoscopy 91% of benign masses.

Study Objective: To evaluate the clinical efficacy and patient satisfaction of long-term danazol delivered vaginally as treatment for heavy menstrual bleeding., Design: Prospective study (Canadian Task Force classification II-3)., Setting: University hospital., Patients: Twenty premenopausal women with endometrial hyperplasia or endometrial polyps., Intervention: After curettage or hysteroscopic-directed biopsies, women used one 200-mg tablet of danazol vaginally every day, continuing the therapy as long as they were totally satisfied with it., Measurements and Main Results: Women were instructed to keep a diary of menstrual bleeding and to rate blood loss on a visual analog scale from zero (no blood loss) to 10 (gushing-type bleeding). They were seen every month for 3 months, then every 3 months for 9 months, and then every 6 months for 4 years for Papanicolau smear, pelvic examination, and transvaginal ultrasonography. They were asked to bring their diary of menstrual bleeding. They were asked about side effects and their satisfaction with the therapy. Peripheral blood was drawn for blood count and serum chemistries. Hysteroscopic-directed biopsies were repeated after 3 months of therapy in women with endometrial hyperplasia. The severity of blood loss was significantly reduced in all women after 3 months of treatment. All women with endometrial hyperplasia had regression of hyperplastic endometrium. None of the women with endometrial polyps had sonographic signs of recurrence during therapy. Only 10 women (50%) completed 1-year follow-up, and only 5 women (25%) completed 5-year follow-up., Conclusion: These results suggest that long-term administration of vaginal danazol after curettage or hysteroscopic-directed biopsy is both efficacious and safe in women with heavy menstrual bleeding, but the rate of discontinuance is high.