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Abstract Background Asthma is a common chronic inflammatory airway affecting over 260 million people worldwide, and characterized, in the large majority of cases, by the so-called “type 2 inflammation”. Fractional exhaled nitric oxide (FENO) testing is noninvasive point-of-care tool to assess type 2 inflammation and therefore improve asthma management. It has been suggested to determine eligibility for a specific biologic therapy and predict likelihood to respond. The aim of this study was to estimate the overall economic impact of an extensive use of FENO testing on the Italian population with asthma, including extra costs of testing and savings generated by more appropriate prescriptions, increased adherence and lower frequency of exacerbations. Methods A cost of illness analysis was firstly performed to estimate the yearly economic burden from the National Healthcare Service (NHS) perspective in Italy of the management of asthmatic patients with standard of care (SOC) according to the application of GINA (Global Initiative for Asthma) guidelines; then, we evaluated the changes in the economic burden in patient management by introducing FENO testing into clinical practice. The cost items considered were: visits/exams, exacerbations, drugs, management of adverse events caused by short-term oral corticosteroids use. Efficacy of FeNO test and SOC is based on literature evidence. Costs refer to published data or Diagnosis Related Group/outpatient tariffs. Results Considering one asthma visit every 6 months, the total yearly cost for the management of patients with asthma in Italy is 1,599,217,876€ (409.07€ per patient), while for FENO testing strategy this figure is 1,395,029,747€ (356.84€ per patient). An increased utilization rate of FENO testing from 50 to 100% of patients may lead to savings for the NHS from about 102 to 204 million € compared to SOC. Conclusions Our study showed that FeNO testing strategy may improve the management of asthmatic patients leading to significant savings for the NHS.

Purpose: To present a modified surgical technique for implantation of the sutureless scleral-fixated hydrophilic intraocular lens (FIL SSF)., Methods: Single surgeon retrospective case series and review of surgical videos with step-by-step technique analysis. Uncorrected and best corrected visual acuity (UCVA and BCVA), refractive error (spherical equivalent), full clinical examination with intraocular pressure (IOP) measurement, endothelial cell density on corneal specular microscopy and macular optical coherence tomography (OCT) were recorded at baseline, 1, 4 and 8 weeks postoperatively., Results: The FIL SSF IOLs were successfully implanted using the so-called "full reverse" technique, having the lens loaded in the injector in an upside-down fashion, as opposed to IOL technical specifications. In all cases, the FIL SSF IOL was properly placed in the ciliary sulcus, well-centered and without signs of tilt. Follow up figures at 2 months are consistent with published data, confirming the potential benefits of the new implantation technique., Conclusion: In our preliminary experience, the "full reverse" technique of the FIL SSF IOL has proven effective in preventing incorrect IOL orientation in 100% of cases. However, larger prospective controlled studies and longer follow up are required to either support or disprove our results., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The aim of this study was to conduct a comparative analysis, using computed tomographic scans, of ossification patterns in unilateral cleft lip and palate patients who underwent early secondary gingivoalveoloplasty (esGAP) versus those who underwent traditional alveolar bone grafting harvested from the iliac crest (IC)., Methods: Computed tomographic scans of 22 consecutively treated patients with esGAP were compared with those of 21 patients treated with bone grafting from the IC. Inclusion criteria were nonsyndromic unilateral cleft lip and palate patients in permanent dentition. Two parameters were considered: the alveolar thickness, measured at 3 levels, and the nasoalveolar height. All measurements were normalized and ratios of the affected versus nonaffected sides were provided as in addition to the statistical comparison between the 2 groups' ossification outcomes., Results: In the esGAP sample, nasoalveolar height was categorized as ideal and good in 86.36% and in 13.64% of the cases, and no mediocre or insufficient ossification was detected; whereas in the bone grafting sample, 38.10% had ideal and good ossification, 14.29% had mediocre ossification, and 9.52% had insufficient ossification. As regards the alveolar thickness, when we consider the average of 3 levels, the esGAP sample was ideal and good in 57.57% and in 30.30% of the cases; for the IC sample, the alveolar thickness was ideal and good 41.27% and in 25.40% of the cases, respectively. The analysis detected a statistically significant difference in the ossification outcomes in the 2 samples., Conclusion: The esGAP yields superior ossification grades in comparison to IC bone grafting., Clinical Relevance Statement: In unilateral cleft lip and palate patients, esGAP seems to allow for a higher grade of ossification compared to IC bone grafting., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

The aim of this study was to investigate differences in mu-wave modulation in individuals diagnosed with autism spectrum disorder (ASD) without intellectual disabilities compared to a group of neurotypical controls (NT). Thirty autistic individuals and 30 NT underwent an EEG recording while watching short videos depicting goal-oriented action filmed from a fixed position, zooming in on the scene, and approaching the scene by means of a steadycam. Then, participants underwent a rating task to evaluate their subjective viewing experience. We found that steadycam videos elicited enhanced event-related desynchronization (ERD), suggestive of enhanced neural activity, in the NT group, and a reduced ERD in the autistic group, compared to the other filming conditions. Autistic participants also showed difficulties in returning to baseline mu-power levels after watching videos filmed from a fixed position. Finally, NT reported feeling more comfortable watching videos with movement, whereas autistic participants did not exhibit differences between conditions. We speculated that static, less naturalistic stimuli might impose higher and prolonged cognitive demands on autistic individuals. Understanding these differences might help develop tailored interventions to support perceptual, cognitive, and social processes of autistic people., (© 2025 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background: With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, we explored the relationships between INSTI/non-INSTI regimens, BMI changes, and DM risk., Methods: RESPOND participants were included if they had CD4, human immunodeficiency virus (HIV) RNA, and ≥2 BMI measurements during follow-up. Those with prior DM were excluded. DM was defined as a random blood glucose ≥11.1 mmol/L, hemoglobin A1c ≥6.5%/48 mmol/mol, use of antidiabetic medication, or site-reported clinical diagnosis. Poisson regression was used to assess the association between natural log (ln) of time-updated BMI and current INSTI/non-INSTI and their interactions on DM risk., Results: Among 20 865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (interquartile range [IQR], 37-52), with a median BMI of 24 kg/m2 (IQR, 22-26). There were 785 DM diagnoses with a crude rate of 0.73 (95% confidence interval [CI], .68-.78)/100 person-years of follow-up. ln(BMI) was strongly associated with DM (adjusted incidence rate ratio [aIRR], 16.54 per log increase; 95% CI, 11.33-24.13; P < .001). Current INSTI use was associated with increased DM risk (IRR, 1.58; 95% CI, 1.37-1.82; P < .001) in univariate analyses and only partially attenuated when adjusted for variables including ln(BMI) (aIRR, 1.48; 95% CI, 1.29-1.71; P < .001). There were no interactions between ln(BMI), INSTI, and non-INSTI use and DM (P = .130)., Conclusions: In RESPOND, compared with non-INSTIs, current use of INSTIs was associated with an increased DM risk, which partially attenuated when adjusted for BMI changes and other variables., Competing Interests: Potential conflicts of interest. V. V., C. C., and L. Y. are employees of ViiV Healthcare, Gilead Sciences, and MSD, respectively. A. R. reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, Pfizer, and Moderna and an investigator initiated trial grant from Gilead Sciences; all remuneration went to his home institution, not to A. R. personally, and all remuneration was provided outside the submitted work. P. E. T.'s institution reports grants and other fees from Gilead Sciences, Merck, and ViiV, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Tuberculosis remains the leading cause of death among people with HIV. The aim of this study was to describe the incidence of tuberculosis (TB), explore risk factors and to calculate their population attributable fractions (PAF) in people with HIV across Europe, stratified by region., Method: Longitudinal study of people with HIV aged>18 years with follow-up from either 1/1/2012, or cohort enrolment, until date of TB diagnosis, last visit, death, or 31/12/2022. Factors associated with TB, in particular antiretroviral therapy status and smoking, were analysed using multivariable Poisson regression., Results: A total of 38 837 participants with HIV with a median follow-up of 7.7 (4.3-10.4) years. Overall, 306 TB cases were diagnosed during 275 811 person-years of follow-up (PYFU; incidence rate (IR) 1.03/1000 PYFU, 95% CI 0.91-1.11). 3.3% ( n =81/2428) participants had incident TB in Eastern Europe (IR 6.13, 4.93-7.62). Overall, the IR decreased from 2.03 (1.53-2.68) in 2012 to 0.44 (0.20-0.97) in 2022. Modifiable risk factors were smoking (adjusted incidence rate ratio 2.94; 95%CI1.62-5.34) and not receiving antiretroviral therapy ( versus on; 3.29; 2.36-4.58). A history of TB pre-baseline increased the risk of recurrence (aIRR 7.77; 95%CI 4.09-14.74). The PAF for not receiving antiretroviral therapy was 34.6% in Non-Eastern Europe and 31.2% in Eastern Europe., Conclusions: TB incidence has been decreasing among people with HIV, but remains more frequent in Eastern Europe. Improvement of antiretroviral therapy-coverage and adherence and a focus on non-communicable disease risk factors such as smoking could reduce the incidence of TB., (Copyright ©The authors 2025. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Computed tomography (CT)-derived low muscle mass is associated with adverse outcomes in critically ill patients. Muscle ultrasound is a promising strategy for quantitating muscle mass. We evaluated the association between baseline ultrasound rectus femoris cross-sectional area (RF-CSA) and intensive care unit (ICU) mortality. Secondary outcomes were the determinants of RF-CSA, and the diagnostic performance of RF-CSA after adjustment for body size., Methods: A prospective, single-center, observational cohort study was conducted in 3 ICUs (general, neuroscience, coronavirus disease-2019 [COVID-19]) of a university-affiliated hospital. Consecutive, mechanically ventilated patients with predicted length of stay >72 hours were included. RF-CSA was assessed at the dominant leg by ultrasound. Association with ICU mortality was tested using multivariable logistic regression. Diagnostic performance of RF-CSA was compared after adjustment by sex (CSA-sex), body surface area (CSA-BSA), and squared height (CSA-H2)., Results: A total of 316 patients were enrolled: age 69 [60-76], 211 men and 183 ICU survivors. Older age (odds ratio, OR [95% confidence interval, CI], 1.03 [1.01-1.05]), the type of ICU (neuroscience: 0.82 [0.38-1.79], COVID-19: 4.1 [2.01-8.38]), a higher modified Nutrition and Rehabilitation Investigators Consortium (NUTRIC) score (1.43 [1.21-1.70]), and a lower RF-CSA (0.41 [0.29-0.58]) were associated with ICU mortality. Baseline RF-CSA was lower in women, with higher nutritional risk, older age, and larger body size. Unadjusted RF-CSA had an area under the receiver operating characteristic (ROC) curve for ICU mortality of 0.720 [0.663-0.776], and this value was not significantly different from that of CSA-sex, CSA-BSA, and CSA-H2 (P = .1487)., Conclusions: Low baseline RF-CSA was associated with increased ICU mortality. Admission RF-CSA was lower in women, with high nutritional risk, in older subjects and with lower body size. Absolute muscle mass was significantly associated with mortality, with no significant increase in this relationship when adjusting for sex or body size., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Importance: During the SARS-CoV-2 pandemic, a complete physical isolation has been worldwide introduced. The impossibility of visiting their loved ones during the hospital stay causes additional distress for families: in addition to the worries about clinical recovery, they may feel exclusion and powerlessness, anxiety, depression, mistrust in the care team and post-traumatic stress disorder. The impossibility of conducting the daily meetings with families poses a challenge for healthcare professionals., Objective: This paper aims to delineate and share consensus statements in order to enable healthcare team to provide by telephone or video calls an optimal level of communication with patient's relatives under circumstances of complete isolation., Evidence Review: PubMed, Cochrane Database of Systematic Reviews, Database of Abstracts and Reviews of Effectiveness and the AHCPR Clinical Guidelines and Evidence Reports were explored from 1999 to 2019. Exclusion criteria were: poor or absent relevance regarding the aim of the consensus statements, studies prior to 1999, non-English language. Since the present pandemic context is completely new, unexpected and unexplored, there are not randomised controlled trials regarding clinical communication in a setting of complete isolation. Thus, a multiprofessional taskforce of physicians, nurses, psychologists and legal experts, together with some family members and former intensive care unit patients was established by four Italian national scientific societies. Using an e-Delphi methodology, general and specific questions were posed, relevant topics were argumented, until arriving to delineate position statements and practical checklist, which were set and evaluated through an evidence-based consensus procedure., Findings: Ten statements and two practical checklists for phone or video calls were drafted and evaluated; they are related to who, when, why and how family members must be given clinical information under circumstances of complete isolation., Conclusions and Relevance: The statements and the checklists offer a structured methodology in order to ensure a good-quality communication between healthcare team and family members even in isolation, confirming that time dedicated to communication has to be intended as a time of care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Receiving communication of positivity for metabolic diseases at Expanded Newborn Screening can be extremely stressful for parents, both in case of false positive and true positive cases. However, little is known about the predictors of distress and differential impact on mothers and fathers., Methods: In this longitudinal study, 169 fathers and 171 mothers referred to one of the Italian metabolic centres for communication of positivity completed a survey including General Health Questionnaire-12, Emotion Thermometers (measuring stress, anxiety, depression, anger and need for help), Impact of Event Scale-Revised, Multidimensional Scale of Perceived Social Support and Emotion Regulation Questionnaire. Perceived severity and control of the children's health were also assessed. The survey was completed in person after the first session at metabolic centres and online after 1, 3 and 6 months., Results: Nearly 80% of parents reported a clinical level of distress and anxiety after the communication of positivity, one-third of them reported post-traumatic symptoms and more than half of parents reported a need for help. After 6 months, there are still more than 30% of parents with a clinical level of distress and anxiety, 6% with post-traumatic symptoms and more than 20% who continue to express a need for help. No gender difference was reported and no differences emerged between pre-COVID-19 and post-COVID-19 periods for parental distress and post-traumatic symptoms.Social support, perceived severity and control of the child's health-but not gender or previous parental experience-predicted the post-traumatic symptoms at baseline while at 6 months the only significant predictor was perceived severity., Conclusion: Adequate psychological support should be provided from the initial communication for both parents and for true positive, false positive and variants of uncertain significance/heterozygous carrier cases., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ Group.)

Purpose: To explore the recalled experience of pregnancy and motherhood in women diagnosed with Autism Spectrum Disorders (ASD) without intellectual disabilities, focusing on sensory perceptions and mood., Methods: We retrospectively evaluated, through an ad-hoc structured interview, the sensory sensitivity during the pre-partum, the peri-partum, and the post-partum of thirty-three mothers with ASD and thirty-two neurotypical mothers. Participants also underwent a psychometric assessment about autistic traits, general sensory sensitivity, and post-partum depressive symptomatology., Results: Mothers with ASD recalled a higher sensitivity than the comparison group across the three time-points; however, during the peri-partum their recalled hypersensitivity decreases, and in the post-partum it returned as high as before childbirth. The difference in the length of recall between groups did not statistically influence our results. Higher levels of autistic traits correlated with higher depressive post-partum symptomatology., Conclusions: Mothers with ASD seem to recall their experience of pregnancy, childbirth, and post-partum period differently from neurotypical mothers, particularly in terms of hypersensitivity. The correlation with depressive symptoms and the potential role of oxytocin and of long-term memory (encoding and recollection) are discussed. Further exploring these aspects might give fundamental hints to provide tailored support to mothers with ASD during pregnancy and motherhood., (© 2023. The Author(s).)

Introduction: Functional Motor Disorder (FMD) is characterized by motor neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. The role of psychological factors in the development, severity, and persistence of FMD remains unclear. We investigated the Attachment State of Mind (SoM) in FMD patients using the Adult Attachment Interview (AAI) and retrospectively examined the quality of their traumatic experiences, if any., Methods: Thirty FMD patients and thirty healthy controls (HC) underwent the AAI and were classified according to both the three-way classification (Free/Secure, Dismissing or Entangled SoM) and the four-way classification (Unresolved SoM, indicating unelaborated traumatic events). Frequency and quality of adverse childhood experiences before the age of 14 were assessed via the Complex Trauma Questionnaire (ComplexTQ)., Results: Among HC, 53.3% exhibited a Free/Secure SoM, while 73.3% of FMD patients displayed an Insecure SoM (Entangled or, primarily, Dismissing). Individuals with Insecure SoM were three times more likely to manifest FMD. Unresolved Trauma was present in 26.7% of HC and 46.7% of FMD patients, with Unresolved Trauma leading to a fourfold increase in the likelihood of manifesting FMD. FMD patients reported significantly higher neglect from both parents, physical abuse from the mother, and parental loss compared to HC., Discussion: Using a gold-standard instrument for evaluating Attachment SoM, we found that FMD patients had a significantly higher prevalence of Insecure SoM and childhood traumatic unresolved events compared to HC, supporting previous literature assessing FMD Attachment Styles through self-report questionnaires. We discuss the potential pathophysiological, neurobiological, and therapeutic implications of our findings., Competing Interests: The authors report no conflict of interest., (© 2024 The Authors.)

Background: Mortality among people with human immunodeficiency virus (HIV) declined with the introduction of combination antiretroviral therapy. We investigated trends in mortality in people with HIV from 1999 through 2020., Methods: Data were collected from the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) cohort between January 1999 through January 2015 and the International Cohort Consortium of Infectious Disease (RESPOND) from October 2017 through December 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV, were calculated. Poisson models were used to assess mortality over time., Results: Among 55 716 participants followed for median 6 years (interquartile range, 3-11), 5263 died (mortality rate [MR], 13.7/1000 person-years of follow-up [PYFU]; 95% confidence interval [CI], 13.4-14.1). Changing mortality was observed: AIDS mortality was most common between 1999-2009 (n = 952; MR, 4.2/1000 PYFU; 95% CI, 4.0-4.5) and non-AIDS-defining malignancy (NADM) between 2010-2020 (n = 444; MR, 2.8/1000 PYFU; 95% CI, 2.5-3.1). In multivariable analysis, all-cause mortality declined (adjusted mortality rate ratio [aMRR], 0.97 per year; 95% CI, .96-.98), mostly 1999-2010 (aMRR, 0.96 per year; 95% CI, .95-.97) but was stable 2011-2020 (aMRR, 1.00 per year; 95% CI, .96-1.05). Mortality due to all known causes except NADM also declined., Conclusions: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts declined between 1999-2009 and was stable over the period 2010-2020. This decline in mortality was not fully explained by improvements in immunologic-virologic status or other risk factors., Competing Interests: Potential conflicts of interest . A. M. reports consulting fees from Eiland and Bonnin. H. F. G. reports honoraria for data and safety monitoring board or advisory board membership from Merck, Gilead Sciences, ViiV Healthcare, GSK, Janssen, Johnson & Johnson, and Novartis; a travel grant from Gilead Sciences; unrestricted research grants from Gilead Sciences; grants or contracts paid to institution from the Swiss National Science Foundation, Swiss HIV Cohort Study, National Institute of Health; and an unrestricted research grant from Gilead Sciences, Yvonne Jacob Foundation. J. J. V. reports personal fees from Merck Sharp & Dohme, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, and APOGEPHA and grants from Merck Sharp & Dohme, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zetrum für Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, and Network University Medicine. F. W. reports personal fees for attending advisory boards from ViiV Healthcare. A. d’A. M. reports fees for lectures sponsored by ViiV, Gilead, and Pfizer and projects sponsored (to institution) by ViiV, Gilead, and Merck Sharpe & Dohme. V. S. reports CME education fees from Gilead Sciences, Merck Sharp & Dohme, and ViiV Healthcare. C. C. reports an unrestricted Nordic Fellowship Grant from Gilead Sciences Nordic; honoraria from GSK and ViiV, Gilead Sciences, and Merck Sharp & Dohme (paid to institution), and has participated on an advisory board for GSK, ViiV and Gilead Sciences (paid to institution). P. S. reports honoraria and/or speaking fees from Gilead, Janssen-Cilag, Merck Sharp & Dohme, Pfizer, and ViiV Healthcare and a research grant from ViiV Healthcare, all outside of the submitted work. A. C. reports consulting fees from Gilead Sciences, Merck Sharp & Dohme, and ViiV Healthcare; honoraria for presentations from Gilead Sciences and ViiV Healthcare; support for travel to advisory board and to study investigator meetings from Merck Sharp & Dohme; and receipt of study medication and supplies from Merck Sharp & Dohme. K. P. reports unrestricted research funding made to institution by Gilead Australia and ViiV Healthcare Australia. F. Bonnet reports grants from Gilead and ViiV Healthcare and honoraria from Gilead, ViiV Healthcare, and Merck Sharp & Dohme. S. D. W. reports payments from the D:A:D and RESPOND studies paid to institution. J. G. is an employee of Gilead Sciences. V. V. is an employee of ViiV Healthcare. L. Y. is an employee of Merck Sharp & Dohme. C. S. reports honoraria for preparation of educational materials from Gilead Sciences and honoraria for speaking and preparation of educational materials from ViiV Healthcare. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: Interest in the well-being of professionals working in psychiatric patient care contexts is growing in the literature. The aim of this study was to explore the perceived role and work experience of psychologist psychotherapists working in Mental Health Centers (MHC)., Methods: A qualitative research was conducted involving psychologists with a training in psychotherapy working in Lombardy who had at least 3 months of working experience in a MHC. A convenience sample was recruited by email through the Order of Psychologists. From November 2022 to March 2023, 3 focus groups were conducted online and were audio-recorded. In each focus group, a video stimulus was shown, followed by questions on the perceived role and work experience of the participants. Three psychologists analyzed the focus groups' transcripts according to thematic content analysis., Results: We enrolled 21 psychologists (3 males, with an average age of 44.71 years (SD=9.09) and with an average of 8.49 (SD=8.81) years of work in MHC). Four themes emerged: epistemology of care, services' organization, role of the psychologist and work experience of the psychologist. Results suggest that the epistemology of care embraced, even implicitly, in the MHC contributes to influence the organization of services, the role of the psychologists and their work experience. In MHCs with a biopsychosocial epistemology, the psychologists felt their role was acknowledged and valued by the care team. This leads to experiences of valorization and appreciation., Discussion and Conclusions: Results highlight the importance of the epistemology of care in influencing organization of services and the perceived role and work experience of the psychologists. However, it is also possible that a more circular relationship between the different levels exists, whereby organizational practices could also influence the epistemology of care and the perceived role and work experience of the psychologist. The variety of experiences, within the same Region, suggest that there is a possible cultural and organizational autonomy in MHCs. A reflection on the epistemology of care and organizational practices adopted in MHCs is needed to promote psychologists' well-being at work.

Anemia is a major complication of chronic kidney disease (CKD). Its prevalence increases with advancing age and progression of kidney disease. The main cause of anemia linked to CKD is represented by the reduction erythropoietin secretion. The increase in cardiovascular risk and mortality is strongly associated with the presence of anemia, and grows with the severity of the anemia, as described in numerous studies. The main therapies for the control of anemia have so far been represented by iron supplementation, the use of synthetic erythropoietin and blood transfusions. Despite the availability of adequate therapies, the prevalence of anemia in CKD continues to be significant. Drugs that inhibit the enzyme prolyl hydroxylase of hypoxia inducible factor (HIF-PHi) are able to mimic a condition of hypoxia and increase the production of endogenous erythropoietin. HIF-PHi therefore represents an important therapeutic alternative for the control of anemia linked to CKD. Numerous studies have confirmed the ability of HIF-PHi to correct anemia and maintain hemoglobin at adequate values; they also highlighted other potential beneficial pleiotropic factors on cholesterol control and iron homeostasis. Further studies are needed to confirm the safety of the drug, especially regarding cardiovascular risk, vascular thrombosis and neoplastic growth. This document highlights the mechanism of action, effects and pharmacological characteristics of HIF-PHi., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Objectives: Tuberculosis (TB) risk after initiation of antiretroviral treatment (ART) is not well described in a European setting, with an average TB incidence of 25/10 5 in the background population., Methods: We included all adult persons with HIV starting ART in the RESPOND cohort between 2012 and 2020. TB incidence rates (IR) were assessed for consecutive time intervals post-ART initiation. Risk factors for TB within 6 months from ART initiation were evaluated using Poisson regression models., Results: Among 8441 persons with HIV, who started ART, 66 developed TB during 34,239 person-years of follow-up (PYFU), corresponding to 1.87/1000 PYFU (95% confidence interval [CI]: 1.47-2.37). TB IR was highest in the first 3 months after ART initiation (14.41/1000 PY (95%CI 10.08-20.61]) and declined at 3-6, 6-12, and >12 months post-ART initiation (5.89 [95%CI 3.35-10.37], 2.54 [95%CI 1.36-4.73] and 0.51 [95%CI 0.30-0.86]), respectively. Independent risk factors for TB within the first 6 months after ART initiation included follow-up in Northern or Eastern Europe region, African origin, baseline CD4 count <200 cells/mm 3 , HIV RNA >100,000 copies/mL, injecting drug use and heterosexual transmission., Conclusions: TB IR was highest in the first 3 months post-ART initiation and was associated with baseline risk factors, highlighting the importance of thorough TB risk assessment at ART initiation., Competing Interests: Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JN received honoraria for presentations from Oxford Immunotec and ViiV and working on the advisory board of Gilead Sciences and ViiV. OK received honoraria for presentations at meetings supported by Merck, unconditional research grants from Gilead and travel support from Gilead and Viiv. HG, JR are employees of ViiV Healthcare, Gilead Sciences, respectively. The remaining authors declared no conflicts of interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Evaluation of 'alternative' vascularisation in human cancer is considered an important prognostic parameter; the 2022 WHO classification of parathyroid tumours despite progresses in clinical triaging of patients strongly emphasises new histopathological parameters to properly stratify these lesions. 'Alternative' and 'classic' vessels were here investigated for the first time in parathyroid tumours for their possible histopathological and clinical relevance during progression., Methods: Using a double CD31/PAS staining, microvessel density (MVD, 'classic' CD31+ vessels), mosaic vessel density (MoVD, 'alternative' CD31+/-vessels) and vessel mimicry density (VMD, 'alternative' CD31-/PAS+ vessels) were evaluated in 4 normal parathyroid glands (N), 50 Adenomas (A), 35 Atypical Tumours (AT) and 10 Carcinomas (K)., Results: Compared with N, MVD significantly increased in A (p=0.012) and decreased in K (p=0.013) with vessel counts lower than in AT and A (p<0.001). MoVs and VMs, absent in normal tissue, were documented in non-benign parathyroid lesions (AT, K) (p<0.001), with MoVs and VMs most represented in AT and K, respectively (p<0.001), in peripheral growing areas. Vessel distribution was correlated to neoplastic progression (r=-0.541 MVD; r=+0.760 MoVD, r=+0.733 VMD), with MVD decrease in AT and K inversely related to MoVD and VMD increase (r=-0.503 and r=-0.456)., Conclusions: 'Alternative' vessel identification in parathyroid tumours is crucial because it: (1) explains the paradox of non-angiogenic tumours, consisting in a new bloody non-endothelial vessel network and (2) helps pathologists to unmask worrisome lesions. Furthermore, detection of alternative vascular systems in human tumours might explain the limited success of antiangiogenic therapies and encourage new oncological studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The implementation of FIT programs reduces incidence and mortality from CRC in the screened subjects. The ultimate efficacy for CRC morbidity and mortality prevention in a FIT program depends on the colonoscopy in FIT+ subjects that has the task of detecting and removing these advanced lesions. Recently, there has been growing evidence on factors that influence the quality of colonoscopy specifically withing organized FIT programs, prompting to dedicated interventions in order to maximize the benefit/harm ratio of post-FIT colonoscopy. This document focuses on the diagnostic phase of colonoscopy, providing indications on how to standardise colonoscopy in FIT+ subjects, regarding timing of examination, management of antithrombotic therapy, bowel preparation, competence and sedation., Competing Interests: Conflict of Interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: While use of some older antiretroviral drugs (ARVs) is associated with chronic liver enzyme elevation (cLEE), the impact of newer ARVs remains unknown., Methods: People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). The primary outcome was first cLEE individuals were censored at first of cLEE, last visit, death, or December 31, 2021. Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6-12 months, 1-2 years, and 2+ years). Poisson regression was used to estimate the incidence rate ratio (IRR) of cLEE and its association with individual ARVs and ARV class., Results: Of 17 106 individuals included contributing 87 924 person-years of follow-up, 1932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0-23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6-12 months: IR, 45.8; 95% CI, 41.4-50.19; 1-2 years: IR, 34.3; 95% CI, 31.5-37.4; and 2+ years: IR, 18.5; 95% CI, 17.4-19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE., Conclusions: cLEE is common and more frequent during the first year after initiating new ARVs. With a >5-year median follow-up, we found no short-term liver safety concerns with the use of INSTIs. Use of NNRTIs and TDF was associated with an increased cLEE risk, while DRV was associated with lower risk., Competing Interests: Potential conflict of interest. M.v.d.V. has received fees for participation in advisory boards and research grants from Gilead, MSD, and ViiV all paid to his institution. H.F.G. has received honoraria for DSMB or advisory board membership from ViiV, GSK, Merck, Gilead, Janssen, Johnson and Johnson, and Novartis. Furthermore, he has received a travel grant from Gilead. Outside of this work, he has received research grants paid to his institution from the Swiss National Science Foundation, Swiss HIV Cohort Study, NIH, Yvonne Jacob Foundation, Gilead, and ViiV. A.M. has received travel support, honoraria, and speaker fees from Gilead, ViiV, and Eiland and Bonnin, all outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Although antibiotic prophylaxis (AB) demonstrated a statistically significant reduction in bacteriuria after invasive urodynamics (UDS), no significant decrease in the incidence of urinary tract infections (UTI) has been confirmed. No absolute recommendations on the use of AB in case of relevant potential risk of UTI have been reported, though some categories of patients at increased infective probability after UDS have been recognized. The aim of this study is to report the experts' consensus on the best practice for the use of AB before UDS in the main categories of patients at potential risk of developing UTI., Materials and Methods: A systematic literature review was performed on AB before UDS in males and females. A panel of experts from the Italian Society of Urodynamics, Continence, Neuro-Urology, and Pelvic Floor (SIUD) assessed the review data and decided by a modified Delphi method on 16 statements proposed and discussed by the panel. The cut-off percentage for the consensus was a ≥70% of positive responses to the survey. The study was a Delphi consensus with experts' opinions, not a clinical trial involving directly patients., Results: The panel group was composed of 57 experts in functional urology and UDS, mainly urologists, likewise gynaecologists, physiatrists, infectivologists, pediatric urologists, and nurses. A positive consensus was achieved on 9/16 (56.25%) of the statements, especially on the need for performing AB before UD in patients with neurogenic bladder and immunosuppression. Urine analysis and urine culture before UDS are mandatory, and in the event of their positivity, UDS should be postponed. A consensus was reached on avoiding AB in menopausal status, diabetes, age, gender, bladder outlet obstruction, high postvoid residual, chronic catheterization, previous urological surgery, lack of urological abnormalities, pelvic organ prolapse, and negative urine analysis., Conclusions: Antibiotic prophylaxis is not recommended for patients without notable risk factors and with a negative urine test due to the potential morbidities that may result from antibiotic administration. However, AB can be used for risk categories such as neurogenic bladder and immunosuppression. The evaluation of urine analysis and urine culture and postponing UDS in cases of positive tests were considered good practices, as well as performing AB in the neurogenic bladder and immunosuppression., (© 2024 Wiley Periodicals LLC.)

Study Question: Does endometriosis prevalence differ in patients with obstructive Müllerian anomalies (OMA) versus those with nonobstructive Müllerian anomalies (NOMA), and in patients with NOMA versus those without Müllerian anomalies?, Summary Answer: The quantitative synthesis of published data demonstrates a substantially increased prevalence of endometriosis in patients with OMA compared with those with NOMA, and a similar prevalence in patients with NOMA and those without Müllerian anomalies., What Is Known Already: The pathogenesis of endometriosis has not been definitively clarified yet. A higher prevalence of endometriosis in patients with OMA than in those with NOMA would support the retrograde menstruation (RM)/implantation theory, whereas a higher prevalence of endometriosis in the NOMA group than in the group without Müllerian anomalies would support the embryonic remnants/celomic metaplasia hypothesis., Study Design, Size, Duration: This systematic review with meta-analysis was restricted to full-length, English-language articles published in peer-reviewed journals between 1980 and 2023. The PubMed and EMBASE databases were searched using the keyword 'endometriosis' in combination with 'Müllerian anomalies', 'obstructive Müllerian anomalies', 'female genital malformations', 'retrograde menstruation', 'infertility', 'pelvic pain', and 'classification'. References from relevant publications were screened, and PubMed's 'similar articles' and 'cited by' functions were used., Participants/materials, Setting, Methods: Studies were selected if they reported the prevalence of surgically confirmed endometriosis in either individuals with OMA compared to those with NOMA, or patients with NOMA compared to those without Müllerian anomalies. Cohort and case-control studies and case series were deemed eligible for inclusion. Noncomparative studies, studies not reporting both the number of individuals with endometriosis and the total number of those with Müllerian anomalies or with other gynecological conditions, those including exclusively data on patients with absent or uncertain menstrual function (e.g. complete Müllerian agenesis category), or with imperforate hymen were excluded. Two reviewers independently abstracted data. The risk of bias was assessed with the Risk of Bias In Non-randomized Studies of Exposures tool. The overall certainty of the evidence was graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines., Main Results and the Role of Chance: Seven retrospective studies were included. The overall mean estimate of endometriosis prevalence was 47% (95% CI, 36-58%) in patients with OMA, and 19% (95% CI, 15-24%) in patients with NOMA, with a common odds ratio (OR) of 4.72 (95% CI, 2.54-8.77). The overall mean estimate of endometriosis prevalence in patients with NOMA was 23% (95% CI, 20-27%), and that in patients without Müllerian anomalies was 21% (95% CI, 20-22%), with a common OR of 0.95 (95% CI, 0.57-1.58). The overall certainty of the evidence according to GRADE guidelines was judged as low for both comparisons., Limitations, Reason for Caution: Some NOMA subtypes may create a partial obstacle to menstrual efflux and/or generate dysfunctional myometrial contractions that favor transtubal reflux, thus increasing the risk of endometriosis and limiting the difference between OMA and NOMA. As infertility and pelvic pain are strongly associated with endometriosis, women with these symptoms are inappropriate controls. Confounding by indication could explain the lack of difference in endometriosis prevalence between patients with NOMA and those without Müllerian anomalies., Wider Implications of the Findings: The results of this meta-analysis support the validity of the RM theory but do not definitively rule out alternative hypotheses. Thus, RM may be considered the initiator for the development of endometriotic lesions, while not excluding the contribution of both inheritable and tissue-specific genetic and epigenetic modifications as disease-promoting factors., Study Funding/competing Interest(s): No funding was received for this review. P.Ve. is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest., Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear., Methods: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality., Results: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies., Conclusions: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM., Competing Interests: Potential conflicts of interest. A. Ma. is full-time employee at Gilead Sciences and owns stock. A. Mo. has received travel support, lecture and consultancy fees from Gilead, ViiV Healthcare, and Eiland and Bonnin, all outside the submitted work. A. E. has received consulting fees and honoraria for lectures and presentations from Roche. C. M. has received honoraria for lectures and presentations from Gilead, ViiV Healthcare, MSD, and travel support from Gilead and a research grant to institution from Gilead. J. J. V. has received honoraria for lectures and presentations from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, Deutsches Zentrum für Infektionsforschung, Uniklinik Freiburg/Kongress und Kommunikation, Akademie für Infektionsmedizin, University Manchester, Deutsche Gesellschaft für lnfektiologie, Ärztekammer Nordrhein, Uniklinik Aachen, Back Bay Strategies, Deutsche Gesellschaft für Innere Medizin, Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, and is part of the data safety monitoring board of APOGEPHA Arznemittel, Biontech, Merck/MSD, Gilead, and Pfizer; and reports research funding from Merck/MSD; Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zetrum für Luft und Raumfahrt (DLR), University of Bristol, Rigshospitalet Kopenhagen. A. C. has received honoraria for lectures and presentation and meetings attendance support from Gilead, ViiV Healthcare, MSD, Janssen-Cilag and is part of the advisory board of Gilead, ViiV Healthcare, MSD and Janssen-Cilag. J. B. has received consulting fees and honoraria for lectures and presentations from ViiV Healthcare, Merck, Gilead, Janssen, Pfizer, and Theratechnology, and honoraria from NovoNordisk and AtraZeneca. S. W. is part of the advisory board of ViiV Healthcare and reports grants or contracts paid to institution from RESPOND. R.M. has received consultancy fees from Tamro Baltics, honoraria honoraria for lectures and presentations from MSD, KRKA, Tamro Baltics, AbbVie and Eurovaistine, payment for expert testimony from Tamor Baltic and meeting attendance support from AbbVie, MSD, Johnson&Johnson, and Swixx BioPharma; and reports unpaid roles as Board member of Lithuanian Infectious Diseases Society and as Scientific committee member of EuroSIDA; and the following grants or contracts unrelated to this work: EuroSIDA/Respond, observational cohort study; WEEPI 1.1, WEEPI 1.2 (Western-Eastern European partnership Initiative on HIV, viral hepatitis and TB). J. T. is a member of the European AIDS Treatment Group, a community organization that receives funding not related to this publication from ViiV Healthcare, Gilead Sciences, MSD, Janssen, Orasure Technologies, European Union (author was paid for project work), Innovative Medicines Initiative, FIND Diagnosis, received consulting fees/honoraria from The Global Fund, UNAIDS, Pan American Health Organization, Frontline AIDS, the Barcelona Institute for Global Health. H. G. is an employee of ViiV healthcare and shareholder of GSK. A.Ma. is an employee and shareholder of Gilead Sciences California. H. C. B. has received in the 36 months prior to the submission of this manuscript one grant from Gilead that was not related to this project. HCB has served as the president of the “association contre le HIV et autres infections transmissibles.” In this role he has received support for the Swiss HIV Cohort Study from ViiV Healthcare, Gilead, BMS, and MSD. M. L. reports paid participation on DSMB with Certa Therapeutics. F.W. reports participation in advisory board for ViiV Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To explore potential alterations of the Body Schema, the implicit sensorimotor representation of one's own body, in patients with Functional Movement Disorders (FMD, Motor Conversion Disorders), characterized by neurological symptoms of altered voluntary motor function that cannot be explained by typical medical conditions. This investigation is prompted by the potential dissociation from their reportedly intact sense of ownership., Methods: 10 FMD patients and 11 healthy controls (HC) underwent the Forearm Bisection Task, aimed at assessing perceived body metrics, which consists in asking the subject, blindfolded, to repeatedly point at the perceived middle point of their dominant forearm with the index finger of their contralateral hand, and a psychometric assessment for anxiety, depression, alexithymia, and tendency to dissociation., Results: FMD patients bisected their forearm more proximally (with an increased shift towards their elbow equal to 7.5%) with respect to HC; average bisection point was positively associated with anxiety levels in the whole sample, and with the tendency to dissociation in the FMD group., Conclusions: FMD patients perceive their forearm as shorter than HC, suggesting an alteration of their Body Schema. The Body Schema can go through short- and long-term updates in the life course, mainly related to the use of each body segment; we speculate that, despite FMD being a disorder of functional nature, characterized by variability and fluctuations in symptomatology, the lack of sense of agency over a body part might be interpreted by the nervous system as disuse and hence influence the Body Schema, as deficits of organic etiology do., Competing Interests: Declaration of competing interest none., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: to analyze the prevalence of ADHD symptoms and traits in a heterogeneous clinical psychiatric sample of young adults (aged 18-24 years old), who referred to a specialized outpatient clinic for various psychiatric and psychological disturbances., Method: 259 participants completed three validated self-report screening questionnaires for ADHD: the Wender Utah Rating Scale (WURS), the Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5 (ASRS-5), and the Conners' adult ADHD rating scale (CAARS)., Results: 12.4% of our sample scored above the cut-off at both the WURS and the ASRS-5 and was considered at risk of ADHD., Conclusion: the prevalence rate in our sample is higher than the one found in the adult general population (6.76%), and in the lower range of the one found in the adult clinical population (6.9%-38.8%). The potential role of sociodemographic (age, sex, gender identity, and employment) and comorbidity factors is discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

According to the International association for the study of pain (Aisd), chronic pain is «an unpleasant sensory and emotional experience associated with, or resembling, ongoing, or potential tissue damage». The evolution of the definition of chronic pain has recognized the centrality of subjective and multidimensional valence, involving biological, psychological, and social aspects. Hence, there is a need to introduce patient-centered medicine and broaden the chronic pain management modalities. The primary clinical goal purpose does not end with the biological dimension and treatment of pain but should include the patient's individual experience and maintain an interdisciplinary value, including pharmacological therapy, as well as psychological care and integrative interventions. The perspectives illustrated provided the theoretical rationale for the organization of the Pain Clinic at Asst Santi Paolo e Carlo University Hospitals in Milan. The articulation of this care pathway can serve as a model, which can be applied to other clinical settings, where an interdisciplinary and multimodal approach is needed.

The Convention on the Rights of Persons with Disabilities (CRPD) enshrines the right of persons with disabilities to enjoy the highest standard of health and access to health care without discrimination, but persons with disabilities have logistical and assistive support needs that must be known in order to build a health service offer that meets their needs and respects their rights in line with the CRPD. Examples of accessibility of medical care include the removal of an architectural barrier, the adaptation of a protocol, and ensuring information about care is delivered using easy to understand means of communications. An example of full inclusion and accessibility of the healthcare system for persons with intellectual disabilities is the DAMA (Disabled Advanced Medical Assistance), a project developed and tested at the Milan San Paolo Hospital. DAMA is an inclusive service provision methodology and offers a model that can follow, with a multidisciplinary approach, the person at every stage of the diagnostic and clinical pathway, and to support his or her family in dealing with the hospital. The diffusion of the DAMA model has demonstrated the flexibility of the model itself and its ability to adapt to hospitals with different characteristics and dimensions. The future is the institution of an organized network of all DAMA centres that share common clinical protocols and homogeneous archives. It will grant us the capability of collecting consistent epidemiological and clinical data, valuable for scientific researching and for training health personnel.

Background: Constipation is frequent in critically ill patients, and potentially related to adverse outcomes. Peripherally-active mu-opioid receptor antagonists (PAMORAs) are approved for opioid-induced constipation, but information on their efficacy and safety in critically ill patients is limited. We present a single-center, retrospective, case-series of the use of naldemedine for opioid-associated constipation, and we systematically reviewed the use of PAMORAs in critically ill patients., Methods: Case-series included consecutive mechanically-ventilated patients; constipation was defined as absence of bowel movements for >3 days. Naldemedine was administered after failure of the local laxation protocol. Systematic review: PubMed was searched for studies of PAMORAs to treat opioid-induced constipation in adult critically ill patients., Primary Outcomes: time to laxation, and number of patients laxating at the shortest follow-up., Secondary Outcomes: gastric residual volumes and adverse events., Key Results: A total of 13 patients were included in the case-series; the most common diagnosis was COVID-19 ARDS. Patients had their first bowel movement 1 [0;2] day after naldemedine. Daily gastric residual volume was 725 [405;1805] before vs. 250 [45;1090] mL after naldemedine, p = 0.0078. Systematic review identified nine studies (two RCTs, one prospective case-series, three retrospective case-series and three case-reports). Outcomes were similar between groups, with a trend toward a lower gastric residual volume in PAMORAs group., Conclusions & Inferences: In a highly-selected case-series of patients with refractory, opioid-associated constipation, naldemedine was safe and associated to reduced gastric residuals and promoting laxation. In the systematic review and meta-analysis, the use of PAMORAs (mainly methylnaltrexone) was safe and associated with a reduced intolerance to enteral feeding but no difference in the time to laxation., (© 2023 John Wiley & Sons Ltd.)

Background: Exclusive enteral nutrition (EEN) is the first choice to induce remission and promote mucosal healing in pediatric Crohn's disease (CD). However, full adherence to EEN treatment may be problematic for children with CD., Methods: The goal of the current multicenter retrospective study was to define predictive factors of nonadherence to treatment and nonremission at the end of induction treatment. Those data together were analyzed with the ultimate goal of trying to define an individualized induction treatment for children with CD., Results: Three hundred seventy-six children with CD from 14 IBD pediatric referral centers were enrolled in the study. The rate of EEN adherence was 89%. Colonic involvement and fecal calprotectin >600 μg/g at diagnosis were found to be associated with a reduced EEN adherence. Exclusive enteral nutrition administered for 8 weeks was effective for inducing clinical remission in 67% of the total cohort. Factors determining lower remission rates were age >15 years and Pediatric Crohn's Disease Activity Index >50., Conclusion: Although EEN is extremely effective in promoting disease remission, several patients' related factors may adversely impact EEN adherence and response. Personalized treatments should be proposed that weigh benefits and risks based on the patient's disease location, phenotype, and disease activity and aim to promote a rapid control of inflammation to reduce long-term bowel damage., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort., Methods: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression., Results: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs., Conclusions: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated., Competing Interests: Potential conflicts of interest. H. A. has received support for attending meetings from Janssen-Cilag, Gilead Sciences and ViiV Healthcare and honoraria for presentations from Gilead Sciences and ViiV Healthcare, outside the present work. A. M. has received payments or honoraria for lectures, presentations and travel support from ViiV Healthcare and Gilead Sciences and consultancy fees as an expert witness for Eiland and Bonnin, outside the submitted work. H. F. G. has received unrestricted research grants and a travel grant from Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, Johnson & Johnson, Janssen, Novartis, GSK and ViiV Healthcare; and grants from the Swiss National Science Foundation, Yvonne Jacob Foundation, and the National Institutes of Health, outside the present work. C.S. reports payment or honoraria for speaking engagements from Gilead Sciences. F. W. reports membership on the advisory board for ViiV. C. L. reports grants or contracts (paid to the institution) from the German federal ministry of education and research, the Federal Joint Committee (Gemeinsamer Bundesausschuss Innovationsausschuss), the Ministerium für Kultur und Wissenschaft in Nordrhein-Westfalen, and the German Center for Infection Research; payment for speaking engagements from Pfizer, ViiV, Gilead, Novartis, MSD, and Biontech; travel support for the 2023 Conference on Retroviruses and Opportunistic Infections (CROI 2023) from Pfizer; and participation on a data safety monitoring or advisory board for ViiV, Pfizer, and Biontech. C. M. reports a research grant from Gilead (paid to the institution), consulting fees (paid to the author) from ViiV, MSD, Gilead, and Janssen, and participation on a data safety monitoring or advisory board for Corimuno. J. C. W. has received payments or honoraria for lectures from Merck Sharp & Dohme. A. S. reports grants or contracts from Gilead Sciences, participation on data safety monitoring or advisory board for GlaxoSmithKline and Gilead Sciences, and a role on the Swedish Reference Group of Antiviral Therapy. C. Smith Stephan has received grants or contracts from the Robert Koch Institute (ClinSurv Steering committee and grant) abd Gesellschaft für Internationale Zusammenarbeit (Hospital Partnership Developing Project [Esther]); consulting fees from Gilead Sciences (speaker fees and advisory board membership) and from Janssen Cilag, Merck Sharp & Dohme, ViiV Healthcare (advisory board membership); payment for expert testimony for Verwaltungsgericht Berlin; and support for attending meetings form Gilead Sciences (Conference on Retrovirus and Opportunistic Infection [American Retrovirus Conference]), Janssen-Cilag (European AIDS Conference travel grant), and AbbVie (Dagnä-Workshop travel grant), outside the present work. K. P. has received grants or contracts from ViiV Healthcare Australia and Gilead Sciences Australia, outside the present work. V. V. is an employee and shareholder of ViiV Healthcare. J. G. is an employee and shareholder of Gilead Sciences. R. M. I. has received payments for presentations in meetings and symposia as a speaker in HIV Clinical Topics (22–23 September 2022; lecture about late human immunodeficiency virus [HIV] presentation) and from the HIV Nordic Symposium (September 2022; role as chairman in a session about long-acting cabotegravir/rilpivirine [GSK]) and reports participation on an advisory board for GSK (November–December 2022) (personal consulting fee in relation to an advisory board regarding new data on dolutegravir-lamivudine and long-acting treatment with cabotegravir-rilpivirine), outside the present work. L. Y. reports other financial or nonfinancial interests with Merck Sharp & Dohme. J. M. L. has received payments or honoraria for lectures, presentations, or speakers bureau participation from Janssen-Cilag, Gilead Sciences, Thera Technologies, and ViiV Healthcare; consulting fees from and participation on a data safety monitoring or advisory board for Janssen-Cilag, Gilead Sciences, and ViiV Healthcare; and support for attending meetings from Gilead Sciences, outside the present work. A.C. reports grants or contracts (paid to institution) from ViiV Healthcare, consulting fees, payment for speaking engagements, and participation on data safety monitoring or advisory boards for Janssen Cilag, Gilead, MSD, and ViiV Healthcare (alls support paid to author). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC)., Patients and Methods: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS)., Results: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59)., Conclusions: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Hereditary polyposis syndromes are a group of inherited disorders associated with a high risk of developing colorectal cancer. The best known ones are familial adenomatous polyposis (FAP), Peutz-Jeghers (PJS), juvenile polyposis and Cowden syndromes, as well as conditions predisposing to cancer, such as Lynch syndrome. Some of them are characterized by an increased risk of small bowel polyps occurrence., Areas Covered: Literature search in PubMed was performed in November 2022 and a narrative review was carried out. Since performing small bowel polypectomy is important in such patients, device assisted enteroscopy (DAE) is the key for this procedure. A screening strategy for small bowel polyps is recommended only for PJS. Guidelines endorse either magnetic resonance imaging (MRI) or videocapsule endoscopy (VCE) every 1-3 years, according to the phenotype of the disease. Enteroscopy should be considered for therapeutic purpose in patients with a positive VCE or MRI. DAE has a central role in the resection of polyps larger than mm or causing symptoms of subocclusion or intussusception. Both single (SBE) and double balloon enteroscopy (DBE) are indicated and able to resect polyps up to 6-10 cm. American guidelines have restricted the indications to small bowel enteroscopy only to FAP patients with grade IV Spiegelman., Expert Opinion: Only some groups of patients (PJS, FAP with demonstrated small bowel polyp burden) may benefit from DAE.

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy., Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website., Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and ≥40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity ( P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001)., Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)

Functional movement disorders (FMD) are characterized by the presence of neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. First evidence showed that, compared to healthy controls (CTR), FMD patients presented increased levels of glutamate+glutamine in the anterior cingulate cortex/medial prefrontal cortex, and decreased levels of glutamate in the cerebrospinal fluid, suggesting that a glutamatergic dysfunction might play a role in FMD pathophysiology. In this study, 12 FMD patients and 20 CTR were recruited and underwent venous blood sampling and urine collection: levels of glutamate, BDNF, dopamine, oxidative stress, creatinine, neopterin, and uric acid were analyzed. Participants also underwent a psychometric assessment investigating depression, anxiety, and alexithymia. We found that levels of glutamate, BDNF, and dopamine were significantly lower in the blood of FMD patients than CTR. Glutamate and dopamine levels were positively associated with levels of alexithymia. Our findings give further evidence that glutamatergic dysfunction might be involved in the pathophysiology of FMD, possibly representing a biomarker of disease; moreover, since glutamatergic and dopaminergic systems are closely interconnected, our results might have a relevance in terms of treatment options for FMD patients., (© 2023. The Author(s).)