[Which non pharmacological interventions should be offered to patients treated with androgen deprivation therapy for prostate cancer? A systematic review]. / Quelles interventions non médicamenteuses proposer aux patients traités par hormono-suppression pour un cancer de la prostate ? Revue systématique de la littérature.

AIM: Prostate cancer is a frequent disease and one of the main treatments used is androgen deprivation therapy, which is a therapy with disabling side effects. Non-pharmacological interventions (NPIs) are evidenced based, non-invasive interventions on human health. They are classified into five categories (physical, psychological, nutritional, digital, elemental). The NPIs sphere is booming and still remains underused in this context. METHODS: A systematic review concerning randomized controlled trials was executed according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the "Medline" and "Kalya Research" databases. After searching and selecting eligible publications, we included 37 randomized controlled trials. RESULTS: The majority of articles concerned physical NPIs with 30 clinical studies, 3 publications dealt with nutritional NPIs, 2 with psychological NPIs and 2 articles concerned elemental NPIs. No publication about digital NPI was found. All of the studies aimed to manage and improve the side effects of treatment. No elemental NPI has demonstrated benefit. Only one psychological NPI and one nutritional NPI were effective. Five types of physical NPI protocols have shown efficacy. The main benefits related to physical abilities, body composition, osteoporosis, quality of life, fatigue, reduced cardiovascular risk and finally anxiety and depression. CONCLUSION: Non-pharmacological interventions, especially physical ones, are effective in managing and reducing the side effects associated with androgen deprivation therapy and should be offered to patients in this context.

Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers.

OBJECTIVE: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline. METHODS: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT). RESULTS: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects. CONCLUSIONS: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.

[Laparoscopic robot-assisted artificial urinary sphincter in women: First approach]. / Sphincter urinaire artificiel robot chez la femme : début d'expérience.

OBJECTIVE OF THE STUDY: To analyze the medium-term results and complications of the artificial urinary sphincter (AUS) AMS 800 implanted using laparoscopic robot surgery in women with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study, which included all procedures done in the CHU of Nîmes from July 2015 to January 2017. Patients with SUI by ISD needing an AUS or patients with a malfunctioning AUS needing to be changed were included. We collected data on intraoperative complications, length of hospitalization, postoperative complications, continence rate at twelve months and satisfaction of patients. RESULTS: Nineteen patients were included, 10 for primo-implantation and 9 for AUS revision. There were 4 postoperative bladder injuries, of which 2 led to laparoconversions. The mean length of hospitalization was 4.1days. Three patients had postoperative complications, which needed an intervention without AUS removal. One patient with persisting SUI due to bladder weakness preferred AUS ablation rather than having a cuff change. There was a median follow-up of 22months (12 to 33months). Sixteen patients out of 19 were completely continent and were satisfied of their intervention and the improvement of their quality of life. CONCLUSION: The laparoscopic robot surgery for AUS implantation is safe and reproducible with good medium-term results. LEVEL OF EVIDENCE: 4.

A Novel Eigenvector-based Method to Detect Mild Alzheimer's Disease Using Event-Related Potentials.

Event-related potentials (ERPs) are a physiological measure of cognitive function that have shown diagnostic and prognostic utility in Alzheimer's disease (AD). In this study, we used a novel eigenvector-based technique to better understand brain electrophysiological differences between subjects with mild AD and healthy controls (HC). Using ERPs from 75 subjects with mild AD and 95 HC, we first calculated cognitive task eigenvectors within each subject from three conditions and then calculated second-order eigenvector components to compare the AD group to the HC group. A MANOVA of the three second-level components discriminated between AD and HC multivariately (Wilks' lambda=.4297, p<0.0001, R2 = .5703), and also on each of the three components univariately (all 3 p-values<0.0001). The eigenvector-based technique used in this study accurately discriminated between the mild AD group and HC. As such, this analysis method adds to our understanding of the differences in ERP signal between AD and HC, and could provide a sensitive biomarker for diagnosis and monitoring of AD progression.

Differential effects of social defeat in rats with high and low locomotor response to novelty.

We compared the response to repeated social defeat in rats selected as high (HR) and low (LR) responders to novelty. In experiment 1, we investigated the behavioral and neuroendocrine effects of repeated social defeat in HR-LR rats. By the last defeat session, HR rats exhibited less passive-submissive behaviors than LR rats, and exhibited higher corticosterone secretion when recovering from defeat. Furthermore, in the forced swim test, while HR defeated rats spent more time immobile than their undefeated controls, LR rats' immobility was unaffected by defeat. In experiment 2, we compared the effects of repeated social defeat on body, adrenal, thymus, and spleen weights in HR-LR rats; moreover, we compared the effects of repeated social defeat on stress related molecules gene expression in these two groups of rats. Our results show that HR rats exhibited a decrease in thymus weight after repeated social defeat that was not present in LRs. Analyses of in situ hybridization results found HR-LR differences in 5-HT(2a) mRNA levels in the parietal cortex and 5-HT(1a) mRNA levels in the dorsal raphe. Moreover, LR rats had higher glucocorticoid receptor (GR) mRNA expression than HR rats in the dentate gyrus, and repeated social defeat decreased this expression in LR rats to HR levels. Finally, hippocampal mineralcorticoid receptor (MR)/GR ratio was reduced in HR rats only. Taken together, our results show a differential response to social defeat in HR-LR rats, and support the HR-LR model as a useful tool to investigate inter-individual differences in response to social stressors.

Differential responses to morphine-induced analgesia in the tail-flick test.

We compared acute and chronic antinociceptive effects of morphine in animals with high reactivity (HR) vs. low reactivity (LR) to novelty. Antinociception was assessed by tail-flick test. Rats were i.p. injected with either saline or morphine (1.5 or 3mg/kg) every 12h for 7 days according to the treatment group. On day 1 of the experiment, LR animals in the 1.5mg/kg morphine group showed significantly higher tail-flick latency than HR. Moreover, significant tolerance to the antinociceptive effects of morphine at the used doses was observed in LR but not HR animals. However, effects of chronic morphine treatment on tail-flick latency in rat groups with similar morphine-induced acute antinociception were undistinguishable. The difference in tail-flick latency between HR and LR rats observed after acute 1.5mg/kg morphine injection was eliminated if beta-funaltrexamine (3mg/kg, i.p.) was administered 24h before the test, an indication that mu opioid receptors are responsible for the difference observed. Studies to anatomically characterize the difference in the acute analgesic effect of morphine in HR vs. LR animals did not however yield any significant difference in mu opioid receptor mRNA levels in locus coeruleus (LC), ventral periaqueductal gray (vPAG), nucleus raphe magnus (NRM) and nucleus reticularis paragigantocellularis (NRPG) between these two groups of animals. In conclusion, our results show that differences in novelty-seeking behavior can predict inter-individual variability in morphine-induced antinociception in rats. Such variability is dependent upon activation of mu opioid receptors, but does not correlate with mu opioid receptor expression in LC, vPAG or ventral medulla.

Inter-individual differences in novelty-seeking behavior in rats predict differential responses to desipramine in the forced swim test.

RATIONALE: Antidepressant medications are effective only in a subpopulation of patients with depression, and some patients respond to certain drugs, but not others. The biological bases for these clinical observations remain unexplained. OBJECTIVE: To investigate individual differences in response to antidepressants, we have examined the effects of the norepinephrine reuptake inhibitor desipramine (DMI) and the selective serotonin reutake inhibitor fluoxetine (FLU) in the forced swim test (FST) in rats that differ in their emotional behavior. METHODS: As response to novelty correlates with numerous other measures of emotionality and substance abuse, we contrasted animals that are high responders (HR) in a novel environment with animals that are low responders (LR) and asked whether the two groups exhibit differential responses to DMI (10mg/kg) and FLU (20mg/kg). RESULTS: At the behavioral level, DMI caused a significant decrease in immobility in LR animals only, while FLU caused a significant reduction in immobility in both groups. Moreover, at the neural level, DMI treatment led to a decrease in FST-induced c-fos messenger RNA levels in medial prefrontal cortex (PFC) and paraventricular nucleus of the hypothalamus (PVN) in LR but not HR animals. CONCLUSIONS: Taken together, our results suggest that the HR-LR model is a useful tool to investigate individual differences in responses to norepinephrine reuptake inhibitors (NRIs) and that a differential activation of PFC and/or PVN could underlie some of the inter-individual differences in the efficacy of NRIs.

ePTFE soft tissue patch reconstruction of hemidiaphragmatic agenesis with late clinical presentation.

In this paper we describe a case of a 71-year-old man affected by left hemidiaphragm agenesis who presented an extensive enterothorax after an asymptomatic history for many years. The patient had late development of severe constipation and occasional episodes of bowel obstruction and vomiting. The surgical correction of this congenital anomaly consisted of restoring the continuity of the diaphragmatic barrier with a 2-mm-thick expanded polytetrafluoroethylene soft tissue patch(Gore-Tex) after the herniated viscera have been replaced into the abdominal cavity. At 26 months' follow-up no recurrence has been observed. We would suggest that this is the first known elderly patient surgically treated and the eighth case reported in the literature. The use of a single-layer ePTFE mesh allows a good anatomical and functional repair. An overview of the literature is also reported.

Anti-C1q antibodies in pregnant patients with systemic lupus erythematosus.

OBJECTIVE: To study anti-C1q antibodies in pregnant patients with systemic lupus erythematosus (SLE) and to evaluate their prognostic significance for the occurrence of disease flares or pregnancy complications. METHODS: Twenty-one pregnancies in 19 SLE patients prospectively followed were analyzed. Disease activity was evaluated on the basis of the physician's intention to treat and a modified version of the ECLAM index. Anti-C1q and anti-dsDNA antibodies were detected in the sera by an ELISA assay. Antinuclear antibodies, anti-ENA antibodies, anticardiolipin antibodies and lupus anticoagulant were also performed. RESULTS: In all the patients the disease was inactive at the beginning of the pregnancy. Four flares of disease activity were observed in 4 pregnancies (19%) and obstetric complications were encountered in 7 pregnancies (43%). Anti-C1q antibodies were positive in 4 (19%) pregnancies and anti-dsDNA antibodies in 8 (38%). The presence of anti-phospholipid antibodies at the first assessment was correlated with the occurrence of obstetric complications (p<0.05). The presence of anti-C1q and anti-dsDNA antibodies at the first assessment had no prognostic significance for the occurrence of flares or obstetric complications during the course of pregnancy. Although the small number of patients studied did not allow for statistically significant analysis, flares appeared to be more likely to occur in patients presenting with anti-dsDNA or anti-C1q antibodies during pregnancy compared to patients with no changes in these antibody titers (43% vs 8% respectively). CONCLUSIONS: The presence of anti-C1q and anti-dsDNA antibodies does not seem to be prognostic for the occurrence of flares during pregnancy. Further studies are warranted to explore this possibility.

New devices for inguinal hernia repair in elderly patients.

A recent meta-analysis concluded that there was a lower incidence of recurrences after mesh hernioplasty, as opposed to non-mesh open methods. Inguinal mesh and plug hernioplasties have been performed using prostheses of different sizes and shapes, either sutured or not to the tissues. However, hernia repair using mesh is sometimes associated with postoperative pain, more or less severe and/or persistent. As a consequence it may interfere with the time required to return to work and to normal daily activities. Finally, concerning the postoperative complications and recurrences, the data presented in our study confirm the very low rate for both aspects; then, as regards the time to return to work, our good results are similar to those of other studies available in literature. In conclusion the tension-free hernia repair described, based upon the use of Prolene 3D patch, is a safe operation, simple to be acquired, it can be performed on an outpatient basis, with a low complication rate, a low level of pain, and an excellent quality of life thereafter. The new device seems to satisfy all requisites of a feasible, reliable and effective system for repairing primary inguinal hernia, at low cost, high patient comfort, and with low risk of recurrences.

Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone.

The function of the second nuclear estrogen receptor, estrogen receptor beta (ERbeta), in the brain is largely unknown. The present study tested whether 1) ERbeta in the paraventricular nucleus (PVN) of the hypothalamus has a direct role in the hypothalamic-pituitary-adrenal (HPA) axis-mediated stress function, and 2) whether corticosterone (CORT) can regulate ERbeta gene expression in the PVN in the intact, cycling female rat. To test the first hypothesis a pure estrogen receptor antagonist, ICI182, 780, was microinjected into the PVN bilaterally and stress-induced CORT response to an acute stressor (15 min restraint) was measured at 0, 15, 30, 60 and 90 min time points. Estrogen antagonist-injected rats showed inhibited CORT levels at the peak (15 min) of the stress response compared with vehicle-injected animals. To test the second hypothesis, ERbeta mRNA levels were measured in the PVN using in situ hybridization histochemistry following sham surgery, adrenalectomy, and adrenalectomy with low or high CORT replacement. Adrenalectomy reduced ERbeta mRNA expression in the PVN, whereas CORT replacement fully reversed this effect in a dose-dependent fashion. Both antagonist inhibition of CORT response and CORT-mediated regulation of ERbeta mRNA were found to be estrus cycle-dependent in the intact, cycling female. These data suggest that ERbeta in the PVN may critically modulate the HPA axis response to stress and is, in turn, regulated by circulating CORT.

Use of gabexate mesylate in Italian hospitals: a multicentre observational study.

INTRODUCTION: Gabexate mesylate has been proposed as a therapeutic or prophylactic agent in a variety of diseases (e.g. disseminated intravascular coagulation, prophylaxis of pancreatic damage and acute pancreatitis), but its clinical effectiveness is still unclear. As the drug is widely used in Italy, we conducted an observational study to determine the pattern of prescription of gabexate in Italian hospitals and to assess the outcome of patients with acute pancreatitis when this treatment is given. An updated meta-analysis of the use of the drug is also presented. MATERIALS AND METHODS: From 20 May to 20 July 2001, all consecutive patients admitted to 13 Italian hospitals were enrolled. The following information was recorded from each patient: indication for the use of gabexate, total dose and duration of gabexate administration, need for surgical treatment and outcome of hospitalization (alive or dead). In the patient subgroup with acute pancreatitis, the outcome data of our observational study were compared with those reported by the randomized trials (RCTs) previously published. For this purpose, the survival data of the RCTs were summarized in an updated meta-analysis. RESULTS: A total of 170 patients were enrolled in the study. The main clinical indications were acute pancreatitis in 88 cases (52%) and prophylaxis of pancreatic damage in 62 cases (36%). At the end of the study, 80 of the 88 patients treated for acute pancreatitis (91%) were alive and eight (9%) had died. In the subgroup of patients with necrotic-haemorrhagic pancreatitis (n = 10), six died during the observation period. Our meta-analysis showed that gabexate mesylate did not improve survival in comparison with placebo. The meta-analytic odds ratio was 0.70 (95% CI: 0.45-1.09). DISCUSSION: The study described the pattern of use of gabexate mesylate in Italian hospitals and provided information on the outcome of the subgroup treated for acute pancreatitis. A meta-analysis of current data from RCTs, together with our findings, indicates that gabexate mesylate does not significantly improve survival in acute pancreatitis.

Modulatory effects of norepinephrine in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress.

The brain noradrenergic system is activated by stress, and modulates the activity of forebrain regions involved in behavioral and neuroendocrine responses to stress, such as the lateral bed nucleus of the stria terminalis (BSTL). This region of the limbic forebrain receives dense noradrenergic innervation, and has been implicated in both anxiety and regulation of the hypothalamic-pituitary-adrenal axis. We hypothesized that stress-induced release of norepinephrine in the BSTL modulates anxiety-like behavioral responses to stress and activation of the hypothalamic-pituitary-adrenal stress axis. Using microdialysis, we showed that release of norepinephrine was increased in the BSTL of male Sprague-Dawley rats during immobilization stress. In the next experiment, we then microinjected noradrenergic antagonists into the BSTL immediately prior to acute immobilization stress to examine noradrenergic modulation of behavioral stress reactivity. Either the alpha(1)-receptor antagonist benoxathian, or a cocktail of beta(1)- and beta(2)-receptor antagonists (betaxolol+ICI 118,551) blocked the anxiety-like reduction in open-arm exploration on the elevated plus-maze, but not the reduction in social behavior induced in the social interaction test. In a third experiment, benoxathian reduced plasma levels of adrenocorticotropic hormone following stress, but beta-receptor antagonists had no effect. From these results we suggest that stress-induced norepinephrine release acts on both alpha(1)- and beta-receptors in the BSTL to facilitate anxiety-like behavioral responses on the plus-maze but not the social interaction test, and modulates hypothalamic-pituitary-adrenal axis activation via alpha(1)-receptors only. Together with previous results in which adrenergic antagonists in central amygdala attenuated behavioral responses on the social interaction test but not the plus-maze, these observations suggest the two behavioral tests measure different dimensions of stress reactivity, and that norepinephrine facilitates different components of the stress response by region- and receptor-specific mechanisms.

Cortical acetylcholine release elicited by stimulation of histamine H1 receptors in the nucleus basalis magnocellularis: a dual-probe microdialysis study in the freely moving rat.

Perfusion of the nucleus basalis magnocellularis (NBM) with histamine agonists and antagonists modulates the spontaneous release of cortical acetylcholine (ACh) in freely moving rats. Perfusion of the NBM with Ringer solution containing 100 mM K+ strongly stimulated the spontaneous release of cortical ACh in freely moving rats, whereas perfusion with 1 microM tetrodotoxin reduced cortical ACh spontaneous release by more than 50%. Administration of histamine to the NBM concentration-dependently increased the spontaneous release of cortical ACh. Administration of H1 (methylhistaprodifen) but not H2 (dimaprit) or H3 (R-alpha-methylhistamine) receptor agonists to the NBM mimicked the effect of histamine. Perfusion of the NBM with either H1 (mepyramine or triprolidine) or H2 (cimetidine) receptor antagonists failed to alter ACh spontaneous release from the cortex, however, H1 but not H2 receptor antagonists antagonized the releases of cortical ACh elicited by histamine and methylhistaprodifen. Local administration of H3 receptor antagonists (clobenpropit and thioperamide) to the NBM increased the spontaneous release of ACh from the cortex; this effect was antagonized by H1 receptor antagonism. Conversely local administration of MK-801, a noncompetitive receptor antagonist of the N-methyl-D-aspartate receptor, to the NBM failed to alter ACh spontaneous release from the cortex and to antagonize ACh release elicited by histamine. This study demonstrates that activation of histamine H1 receptors in the NBM increases ACh spontaneous release from the cortex.

[Adenoid cystic carcinoma of the prostate. Clinical case]. / Carcinoma adenoido-cistico della prostata. Caso clinico.

The authors report an extremely rare case of adenoid cystic carcinoma of the prostate. No satisfactory clinical and pathological classification exists for this tumour, creating particular difficulties for therapeutic decisions and prognosis. Descriptions of cases with excellent survival rates are reported in the literature, to the extent that this is sometimes regarded as a low-malignancy tumour, but other reports also exist of massive diffusion of the pathology with fatal consequences. Advances in the knowledge of this tumour have enabled a number of earlier pathogenetic hypotheses to be ruled out, namely its possible derivation from ectopic salivary cells, ectopic periurethral glands or metaplastic urethral mucosa, but the origin of this carcinoma is still not certain. It is also difficult to differentiate this form from the typical adenocarcinoma and to make a prognosis for survival. In the case reported here, the final diagnosis was made on the lymph node biopsy obtained during surgery, given that a preoperative biopsy was not feasible owing to the scarcity of material available. The patient received standard hormonal therapy for prostate carcinoma.

Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level.

To investigate functional changes in the brain serotonin transporter (SERT) after chronic antidepressant treatment, several techniques were used to assess SERT activity, density, or its mRNA content. Rats were treated by osmotic minipump for 21 d with the selective serotonin reuptake inhibitors (SSRIs) paroxetine or sertraline, the selective norepinephrine reuptake inhibitor desipramine (DMI), or the monoamine oxidase inhibitor phenelzine. High-speed in vivo electrochemical recordings were used to assess the ability of the SSRI fluvoxamine to modulate the clearance of locally applied serotonin in the CA3 region of hippocampus in drug- or vehicle-treated rats. Fluvoxamine decreased the clearance of serotonin in rats treated with vehicle, DMI, or phenelzine but had no effect on the clearance of serotonin in SSRI-treated rats. SERT density in the CA3 region of the hippocampus of the same rats, assessed by quantitative autoradiography with tritiated cyanoimipramine ([(3)H]CN-IMI), was decreased by 80-90% in SSRI-treated rats but not in those treated with phenelzine or DMI. The serotonin content of the hippocampus was unaffected by paroxetine or sertraline treatment, ruling out neurotoxicity as a possible explanation for the SSRI-induced decrease in SERT binding and alteration in 5-HT clearance. Levels of mRNA for the SERT in the raphe nucleus were also unaltered by chronic paroxetine treatment. Based on these results, it appears that the SERT is downregulated by chronic administration of SSRIs but not other types of antidepressants; furthermore, the downregulation is not caused by decreases in SERT gene expression.

[Fibrous pseudotumors of the tunica vaginalis testis. A clinical case]. / Pseudotumore fibroso della tunica vaginale del testicolo. Caso clinico.

A case of multiple fibrous pseudotumors of the tunica vaginalis is reported. Ultrasonography led to diagnosis 10 years previously and the patient underwent surgical exploration when the lesions were up to 6 cm in diameter.

[Prostatic endoprosthesis in the treatment of prostatic obstruction: preliminary experience with the new Trestle model]. / Le protesi endoprostatiche nel trattamento dell'ostruzione prostatica: esperienza preliminare con il nuovo modello Trestle.

The urethral stent is a relatively new treatment modality for benign prostatic hypertrophy ostruction. Although the ultimate prostatic endoprosthesis has yet to be developed, various stents have been produced and investigated with good results. We review the several currently available stents and we report the preliminary clinical experience with a new device (Trestle).