Obesity and sexual health: focus on postmenopausal women.

Menopause is a cardiometabolic transition with many women experiencing weight gain and redistribution of body fat. Hormonal changes may affect also several dimensions of well-being, including sexual function, with a high rate of female sexual dysfunction (FSD), which displays a multifactorial etiology. The most important biological factors range from chronic low-grade inflammation, associated with hypertrophic adipocytes that may translate into endothelial dysfunction and compromised blood flow through the genitourinary system, to insulin resistance and other neuroendocrine mechanisms targeting the sexual response. Psychosocial factors include poor body image, mood disorders, low self-esteem and life satisfaction, as well as partner's health and quality of relationship, and social stigma. Even unhealthy lifestyle, chronic conditions and putative weight-promoting medications may play a role. The aim of the present narrative review is to update and summarize the state of the art on the link between obesity and FSD in postmenopausal women, pointing to the paucity of high-quality studies and the need for further research with validated end points to assess both biomarkers of obesity and FSD. In addition, we provide general information on the diagnosis and treatment of FSD at menopause with a focus on dietary interventions, physical activity, anti-obesity drugs and bariatric surgery.

Sexual functioning in women with functional hypothalamic amenorrhea: exploring the relevance of an underlying polycystic ovary syndrome (PCOS)-phenotype.

PURPOSE: To study sexual function and distress in women with functional hypothalamic amenorrhea (FHA) compared to women with FHA and an underlying polycystic ovary syndrome (PCOS)-phenotype, considering also their psychometric variables. As a secondary aim, we explored the relationship between sexual functioning and hormonal milieu in these women. METHODS: This is a retrospective cross-sectional study conducted on 36 women with typical FHA and 43 women with FHA + PCOS-phenotype. The following validated psychometric questionnaires were administered: Female Sexual Functional Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Body Attitude Test (BAT), Bulimia Investigation Test (BITE), State Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Multidimensional Perfectionism Scale (MPS). Available hormones to formulate FHA diagnosis in the standard routine were considered. RESULTS: Women with typical FHA reported a significantly lower FSFI total score than women with FHA + PCOS-phenotype (95% CI for median 16-21.3 vs. 21.1-24.1, p = 0.002), whereas the FSDS-R score was similar in the two groups (95% CI for median 6-16 vs. 6-16.3). No statistically significant differences were evident in body attitude, state and trait anxiety, depression, bulimic risk, and perfectionism between the two groups, confirming the two FHA groups were superimposable from a psychometric perspective. State anxiety correlated negatively with the FSFI total score in both typical FHA (rho: - 0.33, p = 0.05) and FHA + PCOS-phenotype (rho: - 0.40, p = 0.009). In the entire study population, a positive correlation was found between luteinizing hormone, androstenedione, and 17ß-estradiol and the total FSFI score (rho: 0.28, p = 0.01; rho: 0.27, p = 0.01, rho: 0.27, p = 0.01, respectively). CONCLUSION: Women with FHA showed a very high rate of sexual symptoms as part of their condition, but those with a typical diagnosis displayed a more severe sexual impairment as compared with the FHA + PCOS-phenotype, in spite of a similar psychometric profile. Sexual distress was equally present in both groups (approximately 4 out of 10 women). Further studies should be designed to investigate the potential role of sex hormones, mainly LH-driven androstenedione, in influencing women's sexual functioning.

Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature.

BACKGROUND: P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown. AIM: To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature. METHODS: The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated. RESULTS: Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants. CONCLUSION: This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.

TSH lowering effects of metformin: a possible mechanism of action.

Preliminary clinical evidence suggests that metformin has TSH lowering effects in patients with T2DM and hypothyroidism or in those with TSH serum levels in the upper normal value. Also, metformin may exert a protective role against thyroid nodules growth in patients without insulin-resistance. The cross-talk between tyrosine kinase receptors and the G protein-coupled receptors (which the TSHR belongs to) has been already shown and IRS1 may represent the hub link between TSHR and IR pathways. By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies. However, the existence of this molecular pathway must be confirmed through proper studies and further prospective randomized placebo-controlled studies are needed to confirm this hypothesis.

Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions.

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non-palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non-palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non-palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non-neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6-97.0) and 85.5% specificity (95% CI 75.0-92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9-98.5) and 87.1% specificity (95% CI 70.2-96.4) in discriminating neoplasms from non-neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non-neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non-neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2  = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8-92.0) and 79.1% specific (95% CI 68.3-88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7-69.9) and 100% specific (95% CI 88.8-100) in discriminating non-neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non-neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven.

Activated c-Kit receptor in the heart promotes cardiac repair and regeneration after injury.

The role of endogenous c-Kit receptor activation on cardiac cell homeostasis and repair remains largely unexplored. Transgenic mice carrying an activating point mutation (TgD814Y) in the kinase domain of the c-Kit gene were generated. c-Kit(TgD814Y) receptor was expressed in the heart during embryonic development and postnatal life, in a similar timing and expression pattern to that of the endogenous gene, but not in the hematopoietic compartment allowing the study of a cardiac-specific phenotype. c-Kit(TgD814Y) mutation produced a constitutive active c-Kit receptor in cardiac tissue and cells from transgenic mice as demonstrated by the increased phosphorylation of ERK1/2 and AKT, which are the main downstream molecular effectors of c-Kit receptor signaling. In adult transgenic hearts, cardiac morphology, size and total c-Kit(+) cardiac cell number was not different compared with wt mice. However, when c-Kit(TgD814Y) mice were subjected to transmural necrotic heart damage by cryoinjury (CI), all transgenic survived, compared with half of wt mice. In the sub-acute phase after CI, transgenic and wt mice showed similar heart damage. However, 9 days after CI, transgenic mice exhibited an increased number of c-Kit(+)CD31(+) endothelial progenitor cells surrounding the necrotic area. At later follow-up, a consistent reduction of fibrotic area, increased capillary density and increased cardiomyocyte replenishment rate (as established by BrdU incorporation) were observed in transgenic compared with wt mice. Consistently, CD45(-)c-Kit(+) cardiac stem cells isolated from transgenic c-Kit(TgD814Y) mice showed an enhanced endothelial and cardiomyocyte differentiation potential compared with cells isolated from the wt. Constitutive activation of c-Kit receptor in mice is associated with an increased cardiac myogenic and vasculogenic reparative potential after injury, with a significant improvement of survival.

Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplastic disease. Gemcitabine, the currently used chemotherapeutic drug for PDAC, elicits only minor benefits, because of the development of escape pathways leading to chemoresistance. Herein, we aimed at investigating the involvement of the mitogen activating protein kinase interacting kinase (MNK)/eIF4E pathway in the acquired drug resistance of PDAC cells. Screening of a cohort of PDAC patients by immunohistochemistry showed that eIF4E phosphorylation correlated with disease grade, early onset of disease and worse prognosis. In PDAC cell lines, chemotherapeutic drugs induced MNK-dependent phosphorylation of eIF4E. Importantly, pharmacological inhibition of MNK activity synergistically enhanced the cytostatic effect of gemcitabine, by promoting apoptosis. RNA interference (RNAi) experiments indicated that MNK2 is mainly responsible for eIF4E phosphorylation and gemcitabine resistance in PDAC cells. Furthermore, we found that gemcitabine induced the expression of the oncogenic splicing factor SRSF1 and splicing of MNK2b, a splice variant that overrides upstream regulatory pathways and confers increased resistance to the drug. Silencing of SRSF1 by RNAi abolished this splicing event and recapitulated the effects of MNK pharmacological or genetic inhibition on eIF4E phosphorylation and apoptosis in gemcitabine-treated cells. Our results highlight a novel pro-survival pathway triggered by gemcitabine in PDAC cells, which leads to MNK2-dependent phosphorylation of eIF4E, suggesting that the MNK/eIF4E pathway represents an escape route utilized by PDAC cells to withstand chemotherapeutic treatments.

PATZ1 gene has a critical role in the spermatogenesis and testicular tumours.

PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. To gain insights into its biological role, we generated mice lacking the PATZ1 gene. Male PATZ1(-/-) mice were unfertile, suggesting a crucial role of this gene in spermatogenesis. Consistently, most of adult testes from these mice showed only few spermatocytes, associated with increased apoptosis, and complete absence of spermatids and spermatozoa, with the subsequent loss of tubular structure. The analysis of PATZ1 expression, by northern blot, western blot and immunohistochemistry, revealed its presence in Sertoli cells and, among the germ cells, exclusively in the spermatogonia. Since PATZ1 has been indicated as a potential tumour suppressor gene, we also looked at its expression in tumours deriving from testicular germ cells (TGCTs). Although expression of PATZ1 protein was increased in these tumours, it was delocalized in the cytoplasm, suggesting an impaired function. These results indicate that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mis-localization could be associated to the development of TGCTs.

Emergency gastric ulcer complications in elderly. Factors affecting the morbidity and mortality in relation to therapeutic approaches.

AIM: In elderly the incidence of the emergency gastric ulcer complications, perforation and bleeding are increasing, with a difficult management of these patients for their concomitant diseases. The aim of this work is to analyze the therapeutical approach of emergency gastric ulcer complications in elderly patients, in order to establish the factors affecting the morbidity and mortality. METHODS: Patients older than 70 years, presenting gastric ulcer, observed in a tertiary University Hospital from 1995 to 2003, have been considered for the present study. Two groups of diseases have been examined: ulcer perforation and bleeding ulcer. Age, sex, risk factors, comorbidity, methods of diagnosis, ulcer characteristics, treatment, morbidity, mortality, hospitalization time and follow-up have been considered in each group. RESULTS: Thirteen elderly patients with perforated gastric ulcer have been observed: 9 (69.2%) females and 4 (30.8%) males with a mean age of 80.5 years (range 70-90). Four patients were hospitalized in suburban hospital with an average time between the diagnosis and the surgery of 36 h, while the remnants were hospitalized directly in our Department with a medium waiting time of about 2 h. The surgical procedures were: simple closure with omentum patch in 11 cases (84.6%), and antrectomy in 2 cases (15.4%), in which the antrum was multiply perforated. Two patients presented an ulcer larger than 2 cm treated with simple suture and omental patch without morbidity and mortality. Three patients (23%) died postoperatively, due to septic shock, ventricular fibrillation and intraoperative massive haemorrhage, 2 of these patients came from other hospitals. Twenty-eight elderly patients with bleeding gastric ulcer have been observed during the same period: 13 (46.4%) females and 15 (53.6%) males with a mean age of 79.6 years (range 71-91). Except 2 patients submitted to endoscopic treatment both with adrenaline injection, all the remnant patients were managed with medical therapy (H2-receptor antagonist or proton pump inhibitors and in 7 patients [24.1%] antihaemorrhage drugs), and clinical observation, with a endoscopic control 3-4 days after from the first endoscopy. One of the 2 patients endoscopically treated developed a ulcer perforation after 11 days, and the other one rebled, without possibility of any kind of treatment due to his instable condition of health. Three patients (10.7%) died during their hospital stay not for causes strictly due to the gastric haemorrhage. CONCLUSIONS: Our results suggest that the early diagnoses and early treatment are 2 basic factor on the prognosis of elderly patients with perforated gastric ulcer. The choice between simple closure, with or without vagotomy, or gastrectomy depends from preoperative and operative health conditions of the patient. In patients with ulcer larger than 2 cm, Graham's technique can be performed safely if the preoperative and intraoperative conditions are favourable. Elderly patients with gastric ulcer bleeding show an high risk of morbidity and mortality, related to the risk factors like non steroid anti-inflammatory drugs (NSAIDs) intake or smoke. Repeated endoscopy and antiulcer drugs can manage the high stage patients of Forrest's classification with a low rate of morbidity and mortality. According to literature surgical treatment should be reserved after the second failure of endoscopic treatment.

[Colorectal liver metastases resected with safe margin achieved by tissuelink monopolar floating ball]. / Colorectal liver metastases resected with safe margin achieved by tissuelink monopolar floating ball.

BACKGROUND: Nowadays many technological devices are present in hepatic surgery to permit safer liver resections. Main purpose is decrease the intraoperative blood loss. The aim of this study is to analyze our initial experience in hepatic resections for liver metastasis using the new water-cooled, high-density, monopolar device, the Tissuelink Monopolar Floating Ball and Dissecting Sealer (Tissuelink Medical, Inc., Dover, NH). MATERIALS AND METHODS: We analyzed patients who underwent hepatic surgery for metastases from colorectal cancer between January 2003 and December 2004. Sex, age, type of surgical procedure, duration of the surgical procedure, blood loss, use of vascular clamping of the liver, length of hospital stay, morbidity, and mortality were analyzed. RESULTS: Three liver resection, one segmentectomy and two limited resections were performed with the use of these new devices. In one case the devices was used to increase safe free margin of hepatic resection. Average blood loss was 150 ml (range, 50 to 300 ml). No mortality or morbidity were recorder. CONCLUSIONS: In conclusion, this new device permits a bloodless liver resection avoiding vascular clamping. In plus the effect of radiofrequency waves can be useful to enlarge free resection border in patients submitted to hepatic resection without macroscopically safe margins. Prospective randomized studies are needed in order to establish the effective usefulness.

[Learning curve and early complications of totally implantable venous access devices: is tutoring the solution for the problem?]. / La learning curve e le complicanze immediate dei sistemi totalmente impiantabili venosi: il tutoring come soluzione del problema?

During the last years operators implanting totally implantable venous access devices (TIVADs), type of access, and kind of complications are changed. Aim of this work is to evaluate the incidence of early complications during the learning curve of residents in surgery or inexperienced surgeons, besides considering the tutoring to evaluate its rule to prevent early complications. TIVADs, implanted by residents in surgery or by inexperienced surgeons in the Department of Surgical Science Organ Transplantation and Advanced Technologies of University of Catania from January 1995 to October 2003, have been considered for the present study. Age and sex of the patients, indication, type of surgical access and early complications of the TIVADs have been considered. Early complications are those complications that occur within 30 day after the implant. Ninety-five TIVADs were implanted by surgical approach in 95 patients: 58 males (61%) and 37 females (39%), with a mean age of 55 years (range 31-79). Inexperienced surgeons performed 40 implants (42%) instead resident in surgery implanted 55 TIVADs (58%). The migration out of the vein of a catheter 20 days after the operation was the only complication recorded. TIVADs implant by cut-down technique represent the way to avoid early complications. The learning curve is short and the tutoring is limited at the first phase.

[Importance of nursing in the prevention of complications of totally implantable venous access devices]. / Importanza del nursing nella prevenzione delle complicanze dei sistemi totalmente impiantabili.

The Authors report a case of a patient submitted to chemotherapy that has a complication of its totally implantable venous access device (TIVAD) due to incorrect nursing. The symptoms related to the extravasation of drugs were due to the lateral lesions of the catheter with Huber needle. After X-ray examination the therapy was ablation of the non-functioning device and implant of a new TIVAD. The Authors conclude about careful nursing of the TIVAD in order to avoid further psychological problems in cancer patients.

Laparoscopic resection of an abdominal wall desmoid using a modified suture traction technique: the "marionette trick".

Desmoids are rare mesenchimal tumors that may originate also inside the abdomen or in the abdominal wall. These tumors are biologically characterized by a tendency to local growth, and only rarely are they able to develop distant metastases. Surgical excision usually is the best treatment with a chance of a cure. In the few reports on intraabdominal or abdominal wall desmoids, open surgery always was performed. The first case of successful laparoscopic resection of a symptomatic anterior wall desmoid tumor with intraabdominal growth is reported. During the procedure, it was difficult to mobilize and grasp the mass using the common laparoscopic instruments, but with the help of the "marionette trick," modified suture traction technique, the tumor could be removed easily using only three trocars. With four traction sutures minimizing the wall trauma, the trick made it possible to mobilize the mass in at least, seven directions, according to the principles of physical forces and vectors. This simple trick can be helpful for other common laparoscopic procedures, avoiding the insertion of sometimes ineffective instruments through more traumatic trocars.

Carcinoma alveolar del pulmon. / Alveolar carcinoma of the lung

Se presenta un paciente portador de una neumonitis, que por sus caracteres y por la presencia de un broncograma aereo, desperto la sospecha de un carcinoma alveolar El examen citologico del esputo y el lavado bronquial fue negativo para celulas neoplasicas. Se decidio efectuar una bilobectomia superior y media (derecha) ante la firme presuncion diagnostica de carcinoma alveolar. El estudio histopatologico confirmo el diagnostico. Los autores destacan la escasa frecuencia de este tipo de cancer del pulmon (2 a 4%) y sus caracteristicas clinicas y radiologicas, con el objeto de llamar la atencion sobre esta forma grave del cancer del pulmon y como aporte a la casuistica nacional