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Aim: The purpose of this study was to assess the utility of routine histopathological examination in patients undergoing elective sigmoidectomy for diverticular disease after full colonoscopy 1 year prior to surgery., Methods: We retrospectively analysed medical records of all patients undergoing sigmoidectomy for diverticular disease with a documented colonoscopy within 1 year before surgery from January 2013 to December 2023. We collected preoperative, intraoperative and postoperative data of all patients. The primary endpoint was the percentage of patients with an unexpectedly abnormal histopathological report compared to colonoscopy., Results: During the study period, 207 patients undergoing sigmoidectomy for diverticular disease were included. Mean age was 62.7 ± 13.0 years and 97 (46.9%) patients were men. In eight (3.9%) cases an unexpected finding was noted on the histopathological examination: five (2.4%) of them were hyperplastic polyps with no dysplasia and no clinical relevance, two (1.0%) were polyps with low-grade dysplasia and in one case (0.5%) a diffuse large B-cell lymphoma was present in a patient with history of lymphoma treated in the past 10 years. The Goodman and Kruskal's G index was 0.953 (95% lower limit of 0.913), which indicated high concordance between the colonoscopy and the definitive histopathological examination., Conclusions: In our series, the preoperative colonoscopy reliably predicted the result of the histopathological specimen findings in patients undergoing sigmoidectomy for diverticular disease. Only one (0.5%) high-risk patient had an unexpected clinically significant finding. Therefore, routine histopathological examination may not be justified for all patients., (© 2024 Association of Coloproctology of Great Britain and Ireland.)

This paper presents a comprehensive study of hydrogenated amorphous silicon (a-Si)-based detectors, utilizing electrical characterization, Raman spectroscopy, photoemission, and inverse photoemission techniques. The unique properties of a-Si have sparked interest in its application for radiation detection in both physics and medicine. Although amorphous silicon (a-Si) is inherently a highly defective material, hydrogenation significantly reduces defect density, enabling its use in radiation detector devices. Spectroscopic measurements provide insights into the intricate relationship between the structure and electronic properties of a-Si, enhancing our understanding of how specific configurations, such as the choice of substrate, can markedly influence detector performance. In this study, we compare the performance of a-Si detectors deposited on two different substrates: crystalline silicon (c-Si) and flexible Kapton. Our findings suggest that detectors deposited on Kapton exhibit reduced sensitivity, despite having comparable noise and leakage current levels to those on crystalline silicon. We hypothesize that this discrepancy may be attributed to the substrate material, differences in film morphology, and/or the alignment of energy levels. Further measurements are planned to substantiate these hypotheses.

Objective. Detectors that can provide accurate dosimetry for microbeam radiation therapy (MRT) must possess intrinsic radiation hardness, a high dynamic range, and a micron-scale spatial resolution. In this work we characterize hydrogenated amorphous silicon detectors for MRT dosimetry, presenting a novel combination of flexible, ultra-thin and radiation-hard features. Approach. Two detectors are explored: an n-type/intrinsic/p-type planar diode (NIP) and an NIP with an additional charge selective layer (NIP + CSC). Results. The sensitivity of the NIP + CSC detector was greater than the NIP detector for all measurement conditions. At 1 V and 0 kGy under the 3T Cu-Cu synchrotron broadbeam, the NIP + CSC detector sensitivity of (7.76 ± 0.01) pC cGy -1 outperformed the NIP detector sensitivity of (3.55 ± 0.23) pC cGy -1 by 219%. The energy dependence of both detectors matches closely to the attenuation coefficient ratio of silicon against water. Radiation damage measurements of both detectors out to 40 kGy revealed a higher radiation tolerance in the NIP detector compared to the NIP + CSC (17.2% and 33.5% degradations, respectively). Percentage depth dose profiles matched the PTW microDiamond detector's performance to within ±6% for all beam filtrations except in 3T Al-Al due to energy dependence. The 3T Cu-Cu microbeam field profile was reconstructed and returned microbeam width and peak-to-peak values of (51 ± 1) μ m and (405 ± 5) μ m, respectively. The peak-to-valley dose ratio was measured as a function of depth and agrees within error to the values obtained with the PTW microDiamond. X-ray beam induced charge mapping of the detector revealed minimal dose perturbations from extra-cameral materials. Significance. The detectors are comparable to commercially available dosimeters for quality assurance in MRT. With added benefits of being micron-sized and possessing a flexible water-equivalent substrate, these detectors are attractive candidates for quality assurance, in-vivo dosimetry and in-line beam monitoring for MRT and FLASH therapy., (Creative Commons Attribution license.)

Background: The increasing use of complex and high dose-rate treatments in radiation therapy necessitates advanced detectors to provide accurate dosimetry. Rather than relying on pre-treatment quality assurance (QA) measurements alone, many countries are now mandating the use of in vivo dosimetry, whereby a dosimeter is placed on the surface of the patient during treatment. Ideally, in vivo detectors should be flexible to conform to a patient's irregular surfaces., Purpose: This study aims to characterize a novel hydrogenated amorphous silicon (a-Si:H) radiation detector for the dosimetry of therapeutic x-ray beams. The detectors are flexible as they are fabricated directly on a flexible polyimide (Kapton) substrate., Methods: The potential of this technology for application as a real-time flexible detector is investigated through a combined dosimetric and flexibility study. Measurements of fundamental dosimetric quantities were obtained including output factor (OF), dose rate dependence (DPP), energy dependence, percentage depth dose (PDD), and angular dependence. The response of the a-Si:H detectors investigated in this study are benchmarked directly against commercially available ionization chambers and solid-state diodes currently employed for QA practices., Results: The a-Si:H detectors exhibit remarkable dose linearities in the direct detection of kV and MV therapeutic x-rays, with calibrated sensitivities ranging from (0.580 ± 0.002) pC/cGy to (19.36 ± 0.10) pC/cGy as a function of detector thickness, area, and applied bias. Regarding dosimetry, the a-Si:H detectors accurately obtained OF measurements that parallel commercially available detector solutions. The PDD response closely matched the expected profile as predicted via Geant4 simulations, a PTW Farmer ionization chamber and a PTW ROOS chamber. The most significant variation in the PDD performance was 5.67%, observed at a depth of 3 mm for detectors operated unbiased. With an external bias, the discrepancy in PDD response from reference data was confined to ± 2.92% for all depths (surface to 250 mm) in water-equivalent plastic. Very little angular dependence is displayed between irradiations at angles of 0° and 180°, with the most significant variation being a 7.71% decrease in collected charge at a 110° relative angle of incidence. Energy dependence and dose per pulse dependence are also reported, with results in agreement with the literature. Most notably, the flexibility of a-Si:H detectors was quantified for sample bending up to a radius of curvature of 7.98 mm, where the recorded photosensitivity degraded by (-4.9 ± 0.6)% of the initial device response when flat. It is essential to mention that this small bending radius is unlikely during in vivo patient dosimetry. In a more realistic scenario, with a bending radius of 15-20 mm, the variation in detector response remained within ± 4%. After substantial bending, the detector's photosensitivity when returned to a flat condition was (99.1 ± 0.5)% of the original response., Conclusions: This work successfully characterizes a flexible detector based on thin-film a-Si:H deposited on a Kapton substrate for applications in therapeutic x-ray dosimetry. The detectors exhibit dosimetric performances that parallel commercially available dosimeters, while also demonstrating excellent flexibility results., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Emergency treatment of paraesophageal hernias can be carried out through laparotomy or minimally invasive approaches, however, evidence in this regard is weak. The aim of our study was to assess safety and feasibility of the robotic-assisted treatment of paraesophageal hernias in the emergency setting. At the Bellinzona e Valli Regional Hospital, Switzerland, we conducted a retrospective analysis of patients operated on from January 2020 to January 2024 with robotic surgery for emergency presentation of paraesophageal hernias. Demographic and clinical details, operative techniques, and postoperative outcomes were collected and analyzed. Out of 82 patients who underwent robotic-assisted paraesophageal hernia repair, 17 were treated in the emergency setting. Median age was 79 years (IQR 77-85), 3 (17.6%) patients were male, and median BMI was 23.9 kg/m 2 (IQR 21.0-26.0). Most frequent presentation symptoms were pain (100%), regurgitation (88.2%), and dyspnea (17.6%). No intraoperative complication, conversion to open surgery or stomach resections were recorded. Two complications of grade 3 according to the Clavien-Dindo classification and one of grade 2 occurred; all were successfully treated until resolution. The median length of hospital stay was 8 days (IQR 5-16). After a mean follow-up of 15.9 months (IQR 6.5-25.6) only two small axial asymptomatic recurrences that required no treatment. Despite limitations, our study demonstrated a very low rate of intra- and postoperative complications, likely supporting the safety and feasibility of robotic-assisted treatment for paraesophageal hernias in emergency settings. Larger studies with a control arm are needed to validate our initial findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Robotic-assisted treatment of ventral hernia offers many advantages, however, studies reported higher costs for robotic surgery compared to other surgical techniques. We aimed at comparing hospital costs in patients undergoing large ventral hernia repair with either robotic or open surgery. We searched from a prospectively maintained database patients who underwent robotic or open surgery for the treatment of the large ventral hernias from January 2016 to December 2022. The primary endpoint was to assess costs in both groups. For eligible patients, data was extracted and analyzed using a propensity score-matching. Sixty-seven patients were retrieved from our database. Thirty-four underwent robotic-assisted surgery and 33 open surgery. Mean age was 66.4 ± 4.1 years, 50% of patients were male. After a propensity score-matching, a similar total cost of EUR 18,297 ± 8,435 vs. 18,024 ± 7514 (p = 0.913) in robotic-assisted and open surgery groups was noted. Direct and indirect costs were similar in both groups. Robotic surgery showed higher operatory theatre-related costs (EUR 7532 ± 2,091 vs. 3351 ± 1872, p < 0.001), which were compensated by shorter hospital stay-related costs (EUR 4265 ± 4366 vs. 7373 ± 4698, p = 0.032). In the treatment of large ventral hernia, robotic surgery had higher operatory theatre-related costs, however, they were fully compensated by shorter hospital stays and resulting in similar total costs., (© 2024. The Author(s).)

Background: Few studies assessed robotic in emergency setting and no solid evidence was demonstrated. The aim of this study was to evaluate the feasibility and safety of robot-assisted transabdominal preperitoneal (R-TAPP) repair for the treatment of incarcerated inguinal hernia., Methods: We retrospectively searched from a prospectively maintained database patients who underwent R-TAPP or open surgery for incarcerated inguinal hernias from January 2018 to March 2023. The primary endpoint was to assess safety and feasibility of the R-TAPP compared to the standard approach. For eligible patients, data was extracted and analyzed using a propensity score-matching (PSM)., Results: Thirty-four patients were retrieved from our database, 15 underwent R-TAPP, while 19 underwent open surgery. Mean age was 73.1 ± 14.6 years, 30 patients (88.2%) were male and mean BMI was 23.5 ± 3.2 kg/m 2 . No intraoperative complication occurred. Three cases requiring small bowel resection were all in the open surgery group (p = 0.112). The operative time was 108 ± 31 min versus 112 ± 31 min in the R-TAPP and open surgery groups (p = 0.716). Seven postoperative complications occurred, only one classified as severe was in the open surgery group. The length of hospital stay was 2.9 ± 1.8 in the R-TAPP versus 4.2 ± 2.3 min in the open surgery group (p = 0.077). PSM analysis showed similar postoperative outcomes and costs in both groups., Conclusions: Despite its limitations, our study appears to endorse the safety and feasibility of the robotic-assisted treatment for incarcerated inguinal hernia. This approach yielded comparable results to open surgery, albeit in a limited number of patients, suggesting it might be a viable alternative., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated., Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose arterial oxygen tension to inspiratory oxygen fraction ratio ( P aO 2 / F IO 2 ) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and P aO 2 / F IO 2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge., Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a P aO 2 / F IO 2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (HR 2.38, 95% CI 1.04-5.43; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained prone positioning for ≥3 h·day -1 , no significant differences were found between the two groups (HR 1.77, 95% CI 0.79-3.94; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms in any of the analyses conducted., Conclusions: We observed no clinical benefit from prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest for the present study., (Copyright ©The authors 2023.)

Objective . Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field. Quality assurance dosimetry for MRT must therefore overcome a significant challenge, as detectors require both a high dynamic range and a high spatial resolution to perform accurately. Approach . In this work, a series of radiation hard a-Si:H diodes, with different thicknesses and carrier selective contact configurations, have been characterised for x-ray dosimetry and real-time beam monitoring applications in extremely high flux beamlines utilised for MRT at the Australian Synchrotron. Results . These devices displayed superior radiation hardness under constant high dose-rate irradiations on the order of 6000 Gy s -1 , with a variation in response of 10% over a delivered dose range of approximately 600 kGy. Dose linearity of each detector to x-rays with a peak energy of 117 keV is reported, with sensitivities ranging from (2.74 ± 0.02) nC/Gy to (4.96 ± 0.02) nC/Gy. For detectors with 0.8 μ m thick active a-Si:H layer, their operation in an edge-on orientation allows for the reconstruction of micron-size beam profiles (microbeams). The microbeams, with a nominal full-width-half-max of 50 μ m and a peak-to-peak separation of 400 μ m, were reconstructed with extreme accuracy. The full-width-half-max was observed as 55 ± 1 μ m. Evaluation of the peak-to-valley dose ratio and dose-rate dependence of the devices, as well as an x-ray induced charge (XBIC) map of a single pixel is also reported. Significance . These devices based on novel a-Si:H technology possess a unique combination of accurate dosimetric performance and radiation resistance, making them an ideal candidate for x-ray dosimetry in high dose-rate environments such as FLASH and MRT., (Creative Commons Attribution license.)

Background: Transgender women sex workers (TGW-SW) are disproportionally affected by HIV and have reduced access to testing. Moreover, information regarding their behaviours and health needs is scarce., Methods: A behavioural survey and a targeted testing programme in prostitution sites were conducted in Milan and Monza areas. The non-profit organisation 'ALA Milano Onlus' and 'San Gerardo' Hospital (Monza) implemented a mobile HIV testing unit involving a TGW peer educator, four physicians, a counsellor, a psychologist and a cultural mediator. All TGW-SW were offered anonymous HIV and hepatitis C virus (HCV) oral testing and asked to fill a questionnaire on sexual habits, drug abuse, and knowledge and attitudes towards HIV and STDs., Results: Between May and July 2017, 130 TGW-SW, predominantly migrants, were contacted during 15 street visits; among them, 78 (60%) were interviewed. HIV and HCV testing were accepted by 53 (42%) and 67 (52%) TGW-SW, respectively. Twenty-five (19.8%) subjects who reported already established HIV infection were not retested. Seven patients received a new diagnosis of HIV, while nobody tested positive for HCV. Overall, HIV prevalence was 13.2% (25% including those with already known HIV infection). Recent arrival in Italy and young age were associated with risk of undiagnosed HIV infection. Inconsistent condom use was commonly reported during commercial sex (27%) and with non-commercial partners (64%). Alcohol and cocaine abuse were common problems which facilitated risky behaviours., Conclusions: Oral rapid HIV and HCV testing for TGW-SW in outreach settings were feasible and acceptable and led to a considerable number of new diagnoses. Interventions tailored to TGW-SW, focused on HIV prevention, testing and engagement in care, are fundamental., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The aim of the present study was too investigate prevalence and persistence of human papilloma virus (HPV) and cytological abnormalities (CAs) in the anal swabs of people living with HIV (PLWH): men who have sex with men (MSM), men who have sex with women (MSW) and women (W)., Methods: Between March 2010 and January 2019, an anal swab for cytological and HPV genotyping tests was offered to all PLWH attending our clinic. Logistic regression analysis was conducted to identify predictors of infection., Results: In all, 354 PLWH were screened: 174 MSM, 90 MSW and 61 W. Prevalence of at least one high-risk (HR) HPV was higher in MSM (91%) and W (85%) than in MSW (77%) (P < 0.05). Cytological abnormalities were found in 21.1% of the entire population. At multivariable regression analysis a lower risk for HPV infection was found for W than for MSM [odds ratio = 0.24 (95% confidence interval: 0.115-0.513)] and for MSW than for MSM [0.37 (0.180-0.773)] and there was a significantly higher risk of CAs in PLWH with HPV 16 and 18 [3.3 (1.04-10.49)]. A total of 175 PLWH (103 MSM, 33 MSW and 26 W) had at least one follow-up visit (T1) after a median (interquartile range) follow-up of 3.6 (2.1-5.7) years. The acquisition rate of HR-HPV was high, with 66.7% of PLWH negative for HR-HPV at T0 who became positive at T1 (P < 0.001). The prevalence of CAs was stable (20.6%). A significant association between CAs at T1 and persistence of HPV-16 and/or 18 was found (P < 0.05)., Conclusions: HPV 16 and 18 are associated with the presence and development of CAs irrespective of sexual orientation., (© 2021 British HIV Association.)

Objectives: To evaluate changes in pro-atherosclerotic biomarkers and endothelial function in patients initiating two different PI-based regimens as part of ART., Design: Prospective randomized 24 week study. Treatment-naive HIV-infected patients with CD4+ T cell count >250 cells/mm3 started PI-based regimens including atazanavir/ritonavir (Group A) or lopinavir/ritonavir (Group B) and were followed up in an observational follow-up study until week 96., Methods: The expression of immune activation and adhesion molecules on CD4+ and CD8+ cells and plasma cytokine levels were assessed at weeks 0, 4, 12, 24, 48, 72 and 96. Flow-mediated dilation (FMD), pulse-wave velocity (PWV) and intima-media thickness (IMT) were measured at weeks 0 and 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated., Results: Twenty-seven patients were enrolled, of whom 15 were treated with atazanavir/ritonavir and 12 with lopinavir/ritonavir. After 96 weeks of ART, CD25+/CD8+ T cells and plasma concentration of MCP-1/CCL-2 rose whereas CD44+/CD8+ T cells decreased significantly in both groups. Differences between treatments were noted for HLA-DRII+/CD8+, CD44+/CD4+ and CD11a+/CD4+, with significant increases in Group B versus Group A. No differences between groups regarding IMT, PWV and FMD were found at baseline and week 24., Conclusions: ART initiation with PI-based regimens led to a decrease in pro-atherosclerotic biomarkers at week 24, which then rebounded at week 96. Lopinavir/ritonavir treatment resulted in an unfavourable modulation of such markers compared with atazanavir/ritonavir treatment.

A 50-year-old man was admitted to intensive care unit because of acute respiratory failure due interstitial pneumonia; after admission, a diagnosis of acute human immunodeficiency virus (HIV)-1 infection was made. Clinical and radiological improvement was observed only after introduction of antiretroviral treatment. We discuss the hypothesis of interstitial pneumonia induced by the acute HIV-1 infection.

Background: Tenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear., Methods: Patients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89-60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates)., Results: 2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2-3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8-2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4-6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF., Conclusions: Prompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage., Competing Interests: GL received speaker or consultancy grants from Janssen-Cilag, Gilead and Bristol-Myers Squibb and travel grants from Bristol-Myers Squibb, ViiV and Gilead. FM has served as a consultant on advisory boards for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Tibotec; he has received lecture fees from Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp and Dome, and has received research and educational grants from Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Jansen-Cilag and Roche. RC served as advisor for Gilead and Janssen-Cilag, received speakers’ honoraria from ViiV, Bristol-Myers Squibb, Merck Sharp and Dohme and Janssen-Cilag. NL is member of the advisory board of Abbvie. MdP is member of the advisory boards of Abbvie and Gilead and received speaker grants from Abbvie, Bristol-Myers Squibb and ViiV. SC has been an employee of Gilead between 2012 and 2013, received speaker or consultancy grants from BMS, Abbvie, Gilead and Merck and travel grants from Bristol-Myers Squibb and ViiV. CT is member of the advisory boards of Gilead and ViiV, received research grants from Gilead, speakers grants from Bristol-Myers Squibb, Gilead and ViiV and travel grants from Gilead. AG is member of the advisory boards of Gilead, ViiV, Bristol-Myers Squibb, Janssen-Cilag, Merck Sharp-Dome and Abbvie, received speaker grants from Gilead and travel grants from Gilead, ViiV, Bristol-Myers Squibb, Janssen-Cilag and Merck Sharp-Dome. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Whilst renal dysfunction, especially mild impairment (6090, 60-89, <60 ml/min, was 2.91 (95% CI 2.30-3.67), 4.63 (95% CI 3.51-6.11) and 11.9 (95% CI 6.19-22.85) per 1,000 PYFU respectively, with an unadjusted hazard ratio (HR) of 4.14 (95%CI 2.07-8.29) for patients with eGFR <60 ml/min and 1.58 (95%CI 1.10-2.27) for eGFR 60-89 compared to those with eGFR ≥90. Of note, these estimates are adjusted for traditional cardio-vascular risk factors (e.g. smoking, diabetes, hypertension, dyslipidemia). Incidence of AIDS-related events was 9.51 (95%CI 8.35-10.83), 6.04 (95%CI 4.74-7.71) and 25.0 (95%CI 15.96-39.22) per 1,000 PYFU, among patients with eGFR >90, 60-89, <60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR <60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90

Objectives: We evaluated the possibility that a pattern of abnormal microRNA (miRNA) expression could be fuelling the mechanisms causing HIV-associated lipodystrophy (HAL)., Methods: In this case-control study, samples of subcutaneous adipose tissue from eight consecutive HIV-infected patients on combination antiretroviral therapy with HAL (cases) were compared with those of eight HIV-negative subjects (controls). Human miRNA microarrays were used to probe the transcriptomes of the samples. Analysis of differentially expressed miRNAs was performed using DataAssist v2.0 software, applying a paired Student's t-test., Results: Data showed that 21 miRNAs out of 754 were overexpressed in the patient group. Ten of these (i.e. miR-186, miR-199a-3p, miR-214, miR-374a, miR-487b, miR-532-5p, miR-628-5p, miR-874, miR-125-b-1* and miR-374b*) were up-regulated to a significant degree (fold change >2.5; P < 0.01). Eleven other miRNAs (i.e. miR-let-7d, miR-24, miR-30c, miR-125a-3p, miR-149, miR-191, miR-196-b, miR-218, miR-342-3p, miR-452 and miR-454*) were 2- to 2.5-fold more expressed in HIV+ samples than in controls. Levels of mRNA for lipin 1, the target of miR-218, were significantly lower in subcutaneous adipose tissue from HIV patients., Conclusions: In adipocytes of HIV-infected patients, the up-regulation of specific miRNAs could lead to an increased 'activation' that might contribute to the pathogenesis of HAL by increasing cell turnover and/or promotion of apoptosis., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Human immunodeficiency virus (HIV) infection itself and highly active antiretroviral treatment (HAART) have been proposed to be associated with a higher prevalence of metabolic syndrome, but, to date, prevalence and phenotype of metabolic syndrome among HIV subjects and the related structural and functional vascular alterations are not conclusively defined., Methods: We analyzed the data of 108 HIV-infected subjects without known cardiovascular risk factors: 72 were on HAART (group A, age 46.5±7.5 years, clinical blood pressure 125.7/74.9±11.6/7.8 mmHg) and there 36 in a naïve group (group B, age 40.7±7.9 years, blood pressure 126/75.8±9.8/7.7 mmHg). A total of 224 healthy subjects served as controls (group C, age 44.9±6.9 years, blood pressure 123.7/75.7±9.8/7.1 mmHg). Arterial stiffness was measured by aorto-femoral pulse wave velocity (PWV, sfigmocor), and carotid intima media thickness (IMT) was measured by a semiautomatic echotracking system (Esaote-WTS)., Results: Metabolic syndrome was more frequent in HIV-positive subjects than in controls (19.4%, 13.8%, 4.5% for groups A, B, and C; P<0.001), with no significant difference between HAART and naïve. In metabolic syndrome subjects, group A displayed lipid profile alterations more frequently (91%, 50%, 57% for groups A, B, and C; P<0.05), whereas others metabolic syndrome components were equally represented in the three groups. In metabolic syndrome subjects, IMT was similar [556±108, 542±164, and 564±110.4 μm for groups A, B, and C; P=not significant (NS)], whereas PWV was significantly greater in HAART subjects when compared with controls (10.8±1.8, 9.±1.1, 9.3±1 cm/sec for groups A, B, and C; P=0.02 for A vs. C). Moreover, in this group (metabolic syndrome+HAART), PWV was higher than in subjects on HAART but without metabolic syndrome., Conclusions: HIV subjects showed a higher prevalence and a different pattern of metabolic syndrome components. HAART, more than HIV infection per se, appeared to be responsible for the increased prevalence of metabolic syndrome and arterial function derangement.

Tuberculosis (TB) can develop soon after antiretroviral treatment initiation, as the result of restoration of the anti-TB specific immune response. This form of the disease is often defined as "unmasked TB", and it represents a major challenge for severely immune-suppressed HIV-infected subjects initiating treatment. Emergence of previously unrecognised TB disease occurs frequently in countries where TB/HIV co-infection is common, and where antiretroviral treatment has become increasingly accessible. The challenges posed by unmasked TB, such as its high incidence, the lack of reliable diagnostic tools and the uncertainties on its optimal management, may hamper our ability to face the TB/HIV epidemic. Therefore, unmasked TB appears a major threat to global health and poses additional barriers to successful HIV/AIDS care and treatment programmes. This review focuses on the epidemiology, immunopathogenesis and clinical manifestations of unmasked TB, and provides evidence-based recommendations for management and care of the disease.

Background: Increasing numbers of pregnant HIV-positive women are receiving combination antiretroviral regimens for preventing mother-to-child virus transmission or for treating the infection itself. Several studies have demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxicity by several mechanisms, including depletion of mitochondrial DNA (mtDNA). By the quantification of mtDNA levels, we studied mitochondrial toxicity in HIV-positive women at delivery and the possible correlations with antiretroviral regimens, viroimmunological and metabolic parameters., Methods: We analysed 68 HIV-positive women enrolled in the Italian Prospective Cohort Study on Efficacy and Toxicity of Antiretroviral in Pregnancy (TARGET Study); all were taking ≥1 NRTI. We quantified mtDNA copies per cell in subcutaneous fat samples collected during delivery. At the 3rd, 6th and 9th month of pregnancy, we collected data concerning CD4(+) T-cell count, plasma HIV RNA, total and high-density lipoprotein (HDL) cholesterol, fasting plasma glucose and triglycerides. As a control, we analysed mtDNA levels in abdominal subcutaneous fat samples from 23 HIV-seronegative women at delivery., Results: mtDNA content was significantly lower in HIV-infected women when compared with HIV-negative controls. mtDNA content varied independently from viroimmunological, lipid and glucose parameters at the different months, with the exceptions of triglycerides at the 9th month and of HDL at the 6th month of pregnancy., Conclusions: In subcutaneous tissue from women taking NRTI-based antiretroviral regimens, we observed a significant decrease of mtDNA content, compared with uninfected women not on antiviral treatment. Moreover, a significant correlation was noted between mtDNA content and HDL cholesterol and triglycerides.

Aims: The aim of our study was to measure carotid intima-media thickness (cIMT) and risk factors associated with its development and progression, and to evaluate arterial wall characteristics through integrated backscatter analysis (IBS) in HIV patients., Methods: Perspective cohort study enrolling 44 HIV patients treated with antiretroviral drugs who underwent standard B Mode cIMT measurement and tissue characterization of carotid wall by means of dedicated software by acoustic densitometry, at time 0 and 2 years later., Major Findings: Cross-sectional evaluation performed at baseline found that cIMT value correlated significantly with age (r = 0.42, p = 0.005) and systolic blood pressure (r = 0.31, p = 0.04). No correlation was found between cIMT and CD4, HIV-RNA, triglycerides or total cholesterol. There was no difference between the group with versus the group with no protease inhibitors treatment. cIMT progression during 2 years of observation was statistically significant (median, interquartile range [IQR]: 0.005, 0-0.031). No correlation was found between IBS and duration of disease and kind of therapy, whereas a significant association was found between cIMT and IBS (r = 0.33, p = 0.03). No noticeable changes of IBS were observed during 2 years observation., Conclusions: Classic risk factors greatly affect cIMT than time of HIV infection, duration of antiretroviral therapy exposure and use of protease inhibitors. IBS is a promising technique for the evaluation of arterial wall composition in HIV patients.

Background: Treatment of HIV-infected patients with interleukin-2 (IL-2) produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs)., Methods and Findings: PBMC from 12 immunological non-responders (INRs) (CD4+<200/µl, HIV-RNA<50 cp/ml) on combination antiretroviral treatment (cART) were collected at baseline, and after 3 IL-2 cycles. Eight INRs receiving only cART were studied as controls. After 21 days of PBMC incubation with a virulent M. avium suspension, counts of residual colony forming units (CFUs) and concentrations of TNF-α, IL-10 and IFN-γ were determined. In IL-2 treated patients, a significant reduction in mean residual CFUs of PBMC cultures was observed (p<0.01). Moreover, following IL-2 treatment, significant increases in PBMC's IFNγ production (p = 0.02) and substantial reductions in IL-10 levels were observed., Conclusions: IL-2 therapy restores the ability of the lympho-monocyte system in eliciting an effective response against mycobacterial infections. Our data indicate the possibility of a clinical role held by IL-2 in enhancing the immune function of subjects unable to achieve immune competence through cART alone.

This study was conducted to isolate the needs families express both for medical and psychological care, and for educational and social support in 112 caregivers of patients affected by moderate to severe dementia (mini mental state examination=MMSE score: 9+/-7) consecutively recruited at our Memory Clinic, to develop approaches as individualized as possible. The medical needs caregivers express are mainly relative to a better knowledge of the disease (78%) and the exact diagnosis (65%); the education-related needs are mainly relative to the acquisition of communicational skills (83%) and the optimal handling of cognitive (77%) and behavioral disorders (81%); the psychological ones mainly concern the area of assistance induced emotional stress management (37%) and the elaboration of feelings such as anxiety, rage and guilt (49%). Variance analysis shows a correlation between emotional caregivers' needs and the subjective and objective burdens they carry. Despite the attention to the role families play in caring for patients with a diagnoses of moderate to severe dementia, caregivers still express low levels of illness-consciousness and high levels of psychological discomfort. A lot more ought to be done in order to provide better information about the disease, about appropriate cognitive and behavioral disorder management skills, and about viable psychological support., (Copyright 2009. Published by Elsevier Ireland Ltd.)

Mechanisms by which HIV affects the thymus are multiple and only partially known, and the role of thymic dysfunction in HIV/AIDS immunopathogenesis remains poorly understood. To evaluate the effects of HIV infection on intra-thymic precursors of T cells in HIV-infected adults, we conducted a detailed immunophenotypic study of thymic tissue isolated from 7 HIV-infected and 10 HIV-negative adults who were to undergo heart surgery. We found that thymuses of HIV-infected individuals were characterized by a relative depletion of CD4+ single positive T cells and a corresponding enrichment of CD8+ single positive T cells. In addition, thymocytes derived from HIV-infected subjects showed increased levels of activated and proliferating cells. Our analysis also revealed a decreased expression of interleukin-7 receptor in early thymocytes from HIV-infected individuals, along with an increase in this same expression in mature double- and single-positive cells. Frequency of regulatory T cells (CD25+FoxP3+) was significantly increased in HIV-infected thymuses, particularly in priorly-committed CD4 single positive cells. Our data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4+ T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation.

Long-term efficacy of acetyl-cholinesterase-inhibitor (ACHEI) treatment in mild-to-moderate Alzheimer's disease (AD) is of great relevance for clinical routine and has been investigated over a 21-month period of treatment in a "real word" population. We investigated cognitive (mini mental state examination=MMSE) and functional (instrumental activities of daily living=IADL; activities of daily living=ADL) outcomes in 427 AD patients throughout the above period. At the end of the study, first-time drug takers (naives) declined by 1.2 MMSE points, whereas non-naives by 3.8 points. Predictors of responsiveness for first-time drug takers were MMSE score at baseline and MMSE points gained at 3 months of treatment. Further investigations are needed to shed light on the characteristics of responsiveness to a tailored ACHEI treatment for dementia.

The objective of this study was to evaluate the plasma drug concentrations in human immunodeficiency virus (HIV)-infected pregnant women receiving highly active antiretroviral therapy (HAART) and to define the rate of occurrence of subtherapeutic concentrations for some commonly used antiretroviral drugs during pregnancy. We evaluated HIV-infected women (n = 68) in the third trimester of pregnancy in steady-state treatment with an HAART regimen administrated on a twice a day basis, which included 2 nucleoside reverse transcriptase inhibitors plus nelfinavir (NFV), lopinavir/ritonavir (LPV/r), or nevirapine (NVP). Blood samples were collected at predose (C(trough)). The following thresholds were used to define therapeutic drug concentrations-NFV: 0.8 microg/mL; LPV: 4.0 microg/mL/1.0 microg/mL (experienced/naive); and NVP: 3.1 microg/mL. At predose sampling, adequate drug concentrations were found in a higher proportion of women receiving NFV (70.8%) and LPV (75.0%) than NVP (55.6%). Median C(trough) plasma concentrations were 1.2 microg/mL for NFV, 5.5 microg/mL for LPV, and 3.1 microg/mL for NVP. Women receiving lopinavir/ritonavir had the lowest rates of detectable (>50 copies/mL) HIV RNA (15.4%) compared with rates of 22.2% and 41.7% among women receiving NVP and NFV, respectively. Genotypic resistance was detected in 50% of women with detectable HIV RNA for whom samples were available for testing. Subtherapeutic predose concentrations among HIV-infected pregnant women were more commonly found with NVP than with protease inhibitors. LPV administration was associated with the best viral load suppression.

Background: Liver steatosis is a common finding in hepatitis C virus (HCV) infection and is associated with an increased progression of the disease. However, HCV genotype 3 steatosis presents a peculiar and virus-induced pathogenesis. We analysed the effect of HIV coinfection and antiretroviral therapy on hepatic steatosis and the effect of the steatosis on fibrosis in patients with or without HCV genotype 3 infection., Methods: All consecutive HIV-infected and uninfected patients who had undergone a liver biopsy for evaluation of HCV infection at the Infectious Diseases Clinic (Modena, Italy) were included in this study. Primary outcomes were the presence or absence of steatosis or the presence of moderate or advanced fibrosis., Results: A total of 284 patients were enrolled: 187 infected by HCV and 97 coinfected with HIV and HCV. In HCV genotype 3 patients, only HCV-related variables, such as plasma HCV RNA levels (odds ratio [OR] per log10 1.68, P < 0.001) and estimated duration of HCV infection (OR per year 1.17, P = 0.004) were associated with steatosis. In patients infected with other HCV genotypes, steatosis was associated with older age (OR per 5 years 1.47, P < 0.001), with exposure to d-drugs in HIV-HCV-coinfected patients (OR 2.60, P = 0.04) and specifically exposure to stavudine (OR 2.76 HIV-HCV-coinfected versus not HIV-infected patients, P = 0.04). Steatosis was independently associated with bridging fibrosis only in patients infected by HCV genotype other than 3 (OR 4.03, P = 0.01)., Conclusions: Hepatic steatosis, in both HCV-monoinfected and in HIV-HCV-coinfected patients, is strongly correlated with HCV genotype 3, probably through interactions between HCV virus and liver cells. HIV-related increase of steatosis in patients with HCV is probably related to antiretroviral drugs, especially stavudine, in patients infected by HCV genotype other than 3.

Background: Gastroesophageal reflux disease (GERD) is a chronic disease. Sexual behavior is often altered in chronic illness. The aim of this study was to evaluate sexual behavior in patients affected with GERD before and after medical or surgical treatment in comparison to healthy controls (HC)., Methods: Upper GI endoscopy and 24-h ambulatory pH testing were performed to confirm GERD in symptomatic patients. GERD patients completed an anonymous questionnaire on sexual life before and after medical or surgical treatment., Results: Compared with HC, untreated patients with GERD showed more frequent difficulty in attaining orgasm and painful intercourse. GERD patients after surgical treatment had significantly more difficulty in attaining orgasm, while after continuous medical treatment GERD patients compared with HC had significantly more difficulty in attaining orgasm, higher painful intercourse, lower sexual desire, and perceived more frequently that the partner was unhelpful. When compared with untreated conditions, GERD patients after surgical treatment had a significant improvement in attaining orgasm and in painful intercourse but a significant decrease in sexual desire, a lower satisfaction with their sexual life, and a higher prevalence of an unhelpful partner, whereas GERD patients after medical treatment had a decrease in all indices of sexual behavior., Conclusion: Untreated GERD is associated with disorders in sexual behavior. Compared with HC, only the surgical group partially improved after treatment.

Background and Aims: Postsurgical recurrence (PSR) is common in patients with Crohn's disease (CD) who have undergone surgery. Endoscopy is crucial for the diagnosis of PSR, showing also high prognostic value. Bowel sonography (BS) is accurate for CD diagnosis, but its role in PSR detection and grading has been poorly investigated. The aim of this study was to evaluate the diagnostic accuracy of BS compared to endoscopy in the detection of PSR., Materials and Methods: Between March 2002 and October 2005, to gain evidence of possible PSR, we prospectively performed endoscopy and BS in 45 CD patients who had undergone previous bowel resection. Endoscopy and BS were carried out 1 year after surgery, with diagnosis and grading of PSR made in accordance with Rutgeerts. BS was considered suggestive for PSR in the presence of bowel wall thickness (BWT)>3 mm. Also, an ROC curve was constructed to define the best cutoff value for BWT to differentiate mild from severe PSR (grade 1-2 vs 3-4 of Rutgeerts)., Results: Of the 45 patients with CD, 24 showed endoscopic evidence of PSR (53%). Severe endoscopic PSR was present in 16 patients (66%). Sensitivity, specificity, and positive and negative predictive values of BS were 79%, 95%, 95%, and 80%, respectively, with a sensitivity of 93% for severe PSR. On the ROC curve, a BWT>5 mm showed sensitivity, specificity, and positive and negative predictive values of 94%, 100%, 100%, and 96%, respectively, in differentiating mild from severe PSR, in remarkable agreement with endoscopy (kappa=0.90)., Conclusions: BS shows good sensitivity and high specificity for the diagnosis of PSR in CD, with a BWT>5 mm being strongly indicative of severe endoscopic PSR. Hence, BS could replace endoscopy for the diagnosis and grading of PSR in patients who comply poorly with the endoscopic examination.

Background and Aim: Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are common conditions with some similarities, but different perceptual responses to somatic and visceral stimuli. The purpose of this study was to assess in a large group of IBS patients the somatic perception by transcutaneous electrical nerve stimulation (TENS) and its relation to the level of severity and presence of FMS., Methods: In 99 patients grouped by the validated functional bowel disorder severity index (FBDSI) in mild, moderate, and severe IBS and in 33 healthy controls (HC), we studied discomfort thresholds and perception of somatic stimuli at control (hands and elbows) and active (trapezius) sites by TENS and by using a specific questionnaire., Results: The use of TENS showed that IBS showed significant higher thresholds and lower perception cumulative score compared to HC. The severity of IBS is significantly associated with age and mean control site values for discomfort and borderline associated with gender in the ordinal model constructed for the ascending series protocol. The severity of IBS is also significantly associated with the active cumulative perception score in the long stimulus protocol. Due to limited sample size of IBS men with FMS, analyses of discomfort thresholds and cumulative perception score by FMS were done only for women. IBS women without FMS had significantly higher mean control site values for discomfort and significantly lower active cumulative perception score than HC. IBS women with FMS had significantly lower mean active site values for discomfort thresholds than IBS women without FMS (Dunn's test p < 0.05)., Conclusions: IBS patients showed somatic hypoalgesia to electrical stimuli. The severity of IBS and the presence of FMS influence the perception of somatic stimuli induced by TENS.

Background: Fatigue is reported by many adults at the moment of diagnosis of coeliac disease and during follow-up., Aim: To evaluate the prevalence, characteristics and associations of fatigue in adult coeliac disease patients., Methods: The investigated sample comprised adults from Campania, Italy. A total of 130 coeliac disease patients were consecutively recruited in both treated (59 on gluten-free diet) and untreated conditions (71 on normal diet). The control group was made up of 80 healthy controls. Coeliac disease patients and healthy controls underwent laboratory tests, a set of questionnaires for studying fatigue: visual analogue scale for fatigue, chronic fatigue syndrome questionnaire, fatigue severity scale and a modified version of the Zung self-rating depression scale., Results: Coeliac disease patients showed a significantly lower body mass index than controls (P = 0.0001), lower serum iron (P = 0.04). The entire cohort of coeliac disease patients reported greater modified version of the Zung self-rating depression scale score (P = 0.001), greater visual analogue scale for fatigue score (P = 0.0001) and greater chronic fatigue syndrome questionnaire score (P = 0.0001) compared with healthy controls. Coeliac disease patients on a gluten-free diet had a significantly higher modified version of the Zung self-rating depression scale score than coeliacs on a normal diet (P = 0.001). The prevalence of pathological modified version of the Zung self-rating depression scale score was 17% in all coeliac disease patients and 0% in healthy controls. A significant correlation was found between modified version of the Zung self-rating depression scale score and fatigue scale scores in coeliacs on a normal diet. Presence/absence of gastrointestinal symptoms did not show any significant correlation with modified version of the Zung self-rating depression scale score and fatigue scale scores. In coeliacs on a gluten-free diet, modified version of the Zung self-rating depression scale and fatigue scales scores did not significantly differ from coeliacs on a normal diet and were not related to dietetic compliance., Conclusion: In coeliacs, fatigue is a common finding, which ameliorates with the gluten-free diet and is strictly correlated to depression although coeliacs on a gluten-free diet showed more frequent and more severe depression symptoms than coeliacs on a normal diet.

Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented.

Background: Crohn's disease (CD) is frequently localized in the small bowel, with the diagnosis of disease and the assessment of its extension made by ileo-colonoscopy (IC) and small bowel enteroclysis (SBE). Transabdominal bowel sonography (BS) and Tc-99m-HMPAO leukocyte scintigraphy (LS) are increasingly used for the diagnosis of CD because of their minimal invasiveness, reproducibility, and acceptable costs., Methods: From March 2000 to July 2003, we performed IC, SBE, BS, and LS in 84 patients with either suspected or known small bowel CD., Results: Small bowel CD was present in 50 patients, whereas the other 34 patients received a different diagnosis. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were, respectively, 98%, 97%, 98%, 97%, and 0.97 for SBE; 92%, 97%, 98%, 88%, and 0.94 for BS; and 90%, 93%, 96%, 85%, and 0.92 for LS. In addition, the combined use of BS and LS led to overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 100%, 93%, 96%, 100%, and 0.97, respectively. BS showed a fair concordance with SBE in terms of location (k = 0.71) and a correlation with the extension of the disease (r = 0.67, P < 0.001). LS showed a concordance with SBE with regard to location in about one-half the population (k = 0.54), whereas it was less effective than SBE in defining disease extension., Conclusions: BS and LS are 2 accurate techniques for the diagnosis of small bowel CD, and their combined use can be recommended as an early diagnostic approach to patients in which the disease is suspected. SBE remains the best procedure for the definition of the location and extension of the disease.

Background: Infection with Helicobacter pylori is recognised as a major risk factor for chronic gastritis, peptic ulcer disease and gastric cancer. The association between H. pylori infection and iron deficiency anaemia has been established. Multiple mechanisms have been advocated to explain the relationship between H. pylori and iron status and their association might reduce iron deposit., Aim: Aim of this study was to investigate whether H. pylori infection affects iron absorption., Methods: The study was designed on a prospective basis. Fifty-five subjects underwent upper gastrointestinal endoscopy and biopsy to investigate the presence of H. pylori and, when this was positive, also search of serum anti-CagA was performed. Tests included an oral iron absorption test with the administration of 1 mg/kg of Fe2+. Iron levels were measured before and 2 h after iron administration (delta iron). H. pylori-positive subjects were administered antibiotic therapy for 1 week and, 2 months later, the oral iron absorption test was repeated and urea-breath test was first performed., Results: H. pylori-positive subjects had lower serum level of ferritin and lower delta iron compared to H. pylori-negative subjects. That difference is significant in anaemic women and is independent of the presence of serum anti-CagA antibodies. After H. pylori eradication iron absorption test was similar to those of non-infected subjects., Conclusion: H. pylori infection impairs iron uptake. That mechanism, together with others, may contribute to the depletion of iron in infected patients.

Background: Celiac disease is considered to arise from an inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed people, whereas the T(H)2-type lymphocytes are mostly involved in IgE-mediated reactions. The matter of possible coexistence of T(H)1- and T(H)2-type diseases is still debated., Objective: This study was aimed to evaluate the allergy prevalence in a large series of adults with untreated celiac disease and their families at the moment of diagnosis. We also evaluated whether 1 year of gluten-free diet had any effect on allergy prevalence in our cohort., Methods: At the moment of celiac disease diagnosis a standardized questionnaire was administered for detailed information on presence and type of any allergy symptoms in 1044 adult patients with celiac disease, 2752 relatives, and 318 spouses. Those reporting any allergy underwent tests with dosage of serum levels of total IgE and search for serum specific IgE with a standard makeup of 20 antigens and PRICK tests in selected individuals. At follow-up visit patients with celiac disease were administered the same allergy questionnaire., Results: One hundred seventy-three patients with celiac disease (16.6%), 523 relative (19%), and 43 spouses (13.5%) had at least 1 allergy (P=not significant). Atopic dermatitis was more frequent in patients with celiac disease (3.8%) and their relatives (2.3%) than in spouses (1.3%). The presence of allergy in general and atopic dermatitis was not affected by presence of overt malabsorption or duration of undiagnosed disease. Follow-up data showed no change in allergy prevalence in the cohort examined., Conclusion: Allergy prevalence in a large series of patients with celiac disease is not different from that of their relatives and spouses. However, atopic dermatitis was about 3 times more frequent in patients with celiac disease and 2 times more frequent in their relatives than in spouses. One year of gluten-free diet did not change allergy prevalence in the celiac group under investigation.

Following the recent disclosure (Part I of this paper) of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) amides and of their improved pharmacokinetic profile with respect to the originally reported esters, a further exploration of the C-2 position through a solid-phase approach is reported here.

Introduction: Untreated coeliac disease may induce malabsorption of many nutrients. It may also induce vitamin K deficiency, which causes prolongation of the prothrombin time. The aim of the present study was to evaluate the prevalence and associations of prolonged prothrombin time in a series of coeliac adults., Methods: We carried out a cross-sectional analysis of data collected on 390 adults with untreated coeliac disease diagnosed from January 1997 to December 2000. Prolonged prothrombin time was defined as INR > or = 1.4., Results: A prolonged prothrombin time was found in 72 coeliac patients (18.5%). Parenteral vitamin K therapy was required in 5.6% of patients. Patients with prolonged prothrombin time had significant lower values of haemoglobin, iron, proteins, cholesterol and serum aspartate transaminase, and significantly higher prevalence of diarrhoea, weight loss, abdominal pain and low bone mineral density in comparison with patients with normal prothrombin time. However, low bone density was present in 11.6% of patients with normal INR. A prolonged prothrombin time was only found in a few patients with subclinical coeliac disease (0.9%)., Conclusions: Data indicate that the prevalence of prolonged prothrombin time is about 20% in a large series of adult untreated coeliac patients. A prolonged prothrombin time was significantly related to all the markers of severe malabsorption, including low mineral density. Our suggestion is that vitamin K related proteins may also play a role in determining or worsening calcium homeostasis disorders in coeliac disease. The very low prevalence of coagulation disorders in subclinical coeliac disease indicates that there is no need to screen for coeliac disease in patients with isolated coagulation disorders.

To identify neuroprotective agents after stroke, new substituted tetrahydroquinoline derivatives were designed as antagonists of the glycine binding site associated to the NMDA receptor, satisfying the key pharmacophoric requirements. In particular, the racemate 3c exhibited outstanding in vivo activity in the MCAo model in rats, when given iv both pre- and post-ischemia. Pure enantiomers 3c-(+) and 3c-(-) have been prepared following an original synthetic route. Despite the significant difference of activity observed in vitro, they shown similar neuroprotective profile in the MCAo model in rats.

Background: The relation between gastro-esophageal reflux disease (GERD) and obesity is controversial. The laparoscopic adjustable gastric band (LAGB) procedure is effective for morbid obesity. Its indication in the presence of GERD, however, is still debated. This study aimed to investigate esophageal symptoms, motility patterns, and acid exposure in morbidly obese patients before and after LAGB placement., Method: For this study, 43 consecutive obese patients were investigated by a standardized symptoms questionnaire, stationary manometry and 24-h ambulatory pH-metry, and 16 patients with abnormal esophageal acid exposure were reevaluated 18 months after LAGB placement., Results: Symptom scores and abnormal esophageal acid exposure were found to be significantly higher, Lower Esophageal Sphincter (LOS) pressure was significantly lower in obese patients than in control subjects. After LAGB, esophageal acid exposure was significantly reduced in all but two patients, who presented with proximal of gastric pouch dilation., Conclusions: There is a high prevalence of GERD in the obese population. Uncomplicated LAGB placement reduces the amount of acid in these patients with abnormal esophageal acid exposure.

Gastrointestinal involvement is frequent in patients with systemic sclerosis (SSc); however, studies on the proximal stomach and its regulation are lacking. It has been hypothesized that the primary event in the pathogenesis of gastrointestinal involvement in SSc is an early neural lesion. This study investigates proximal stomach function and its relation to autonomic nerve function in SSc. Twenty SSc patients classified in to clinical subsets, underwent measurement of proximal stomach function with and without glucagon by electronic barostat and an assessment of autonomic nerve function. SSc patients were not significantly different from 11 controls for gastric compliance (59.5+/-5.0 vs 47.7+/-4.2 ml/mm Hg, P = 0.1). The pressure-volume curves in each participant with and without glucagon were significantly different (P < 0.001). A significant positive association was found between gastric compliance and autonomic nerve function (P < 0.05). The change in gastric compliance during glucagon administration was significant-associated with autonomic function (P < 0.05). The perception cumulative scores did not differ between SSc patients and control subjects (P = 0.2). In conclusion, proximal stomach function is associated with autonomic nerve function in SSc patients. This confirms the frequent association of motility disorders with autonomic dysfunction in SSc.

A series of analogues of the indole-2-carboxylate GV150526, currently in clinical trials as a potential neuroprotective agent for the control of the cerebral damage after stroke onset, was designed based on previous studies dealing with the electronic features of the north-east region of the glycine binding site associated with the NMDA receptor. In particular, the substitution of the para position of the terminal phenyl ring of GV150526 with suitable hydrophilic groups resulted in the identification of a new class of glycine antagonists. These compounds exhibited nanomolar in vitro affinity to the glycine binding site, high receptor selectivity, and outstanding in vivo potency. In particular, 3-[(E)-2-[(4-ureidomethylphenyl)aminocarbonyl]ethenyl]-4, 6-dichloroindole-2-carboxylic acid was found to be highly effective in the middle cerebral artery occlusion (MCAo) model in the rat, an animal model of focal ischemia, when given both prior to and after the occlusion of the middle cerebral artery. Notably, a significant neuroprotective effect was seen in this model postischaemia, when the administration of this compound was delayed up to 6 h from the occlusion of the middle cerebral artery, further confirming the wide therapeutic window seen for GV150526A.

Background: Esophageal reflux is common in obese patients. Hiatal hernia is considered a potential contraindication to placement of a Lap-Band., Methods: Esophageal investigation in patients who were candidates for a Lap-Band included clinical evaluation of symptoms (scoring system), endoscopic and radiologic evaluation, 24-h pH test, and stationary manometry. Patients with gastroesophageal reflux (GER) with or without hiatal hernia underwent the Lap-Band procedure., Results: GER was diagnosed in 12/40 morbidly obese patients, 11 of whom received a standard Lap-Band (3 patients were radiologically diagnosed with transient hiatal hernia). One patient with a large hiatal hernia underwent closure of the diaphragmatic esophageal hiatus, and the Lap-Band was positioned similarly to an Angelchik prosthesis. All but 1 patient who was lost at follow-up were symptom-free (range 1-24 months)., Conclusion: GER with or without hiatal hernia is not a contraindication for obese patients undergoing a Lap-Band procedure. It accomplishes by a single operation satisfactory treatment of these two disturbing diseases.

Background: Sexual behaviour is often altered in chronic illness., Aim: To evaluate sexual behaviour in coeliac patients before and after treatment with a gluten-free diet., Patients: Fifty-five adults with coeliac disease and 51 age- and sex-matched healthy controls., Methods: Routine clinical and laboratory work-up was used for diagnosis of coeliac disease. Age of first sexual intercourse, prevalence of individuals who were sexually active, frequency of intercourse, reduction in sexual desire, difficulty in attaining orgasm, pain during intercourse, and prevalence of individuals defining themselves as satisfied with their sexual life were investigated by an anonymous, self-administered questionnaire administered before and after one year's treatment with a gluten-free diet in coeliac patients, and only once in controls. Analyses included clinical conditions, demographic and socio-economic data., Results: Compared with controls, untreated coeliac patients had a significantly lower frequency of intercourse and a lower prevalence of individuals satisfied with their sexual life. Patients with overt and subclinical coeliac disease did not show significant differences for any indices of sexual behaviour. Compared with untreated conditions, coeliac patients after one year of treatment had improved values for all indices of sexual behaviour: differences were significant for frequency of intercourse and prevalence of individuals satisfied with their sexual life., Conclusion: Untreated coeliac disease, even in its subclinical presentation, is associated with disorders in sexual behaviour which are improved by the dietary treatment.

Objective: A high prevalence of reflux esophagitis in celiac children and gut motor disorders in adult patients have been described. The aim of this study is to investigate the prevalence of esophageal symptoms and the esophageal motility pattern in adult celiac patients before and after gluten-free diet., Methods: In 22 consecutive adult celiac patients, before and after gluten-free diet, and in controls we calculated an esophageal symptom score regarding heartburn, regurgitation, dysphagia, and chest pain, and performed esophageal manometry using a constantly perfused multilumen catheter., Results: Patients were divided into two groups: with and without steatorrhea. Before gluten-free diet, the prevalence of esophageal symptoms was 45.5 % in all patients, but was significantly higher in patients with steatorrhea than in those without and in 44 control subjects (80% vs 16.7% and 27%, p < 0.05). Lower esophageal sphincter pressure was 17.5+/-5.3 in all patients, but was significantly lower in patients with steatorrhea than in patients without steatorrhea and 11 controls subjects (13.1+/-4.1 vs 21.0+/-2.9 and 20.7+/-3.7 mm Hg (mean+/-SD, p < 0.05). After the diet, the prevalence of esophageal symptoms diminished in all patients (9% vs 45.4%, p < 0.05) and lower esophageal sphincter pressure, measured in 13 patients, increased (19.0+/-3.7 vs 15.7+/-5.3 mm Hg, p < 0.05)., Conclusion: Adult celiac patients with steatorrhea present a higher prevalence of esophageal symptoms and a lowered lower esophageal sphincter pressure compared with celiac patients without steatorrhea and control subjects, but these phenomena can be reverted to control levels by gluten-free diet.

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42 +/- 15 years, mean +/- SD), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8 +/- 2.3 vs placebo: 2.8 +/- 1.6; P < 0.002) and a significant decrease in straining at defecation (P < 0.01), stool consistency (P < 0.02), and use of laxatives (P < 0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.