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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.

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.

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.