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Introduction According to current diagnostic systems, affective symptoms do not represent a fundamental criterion for the diagnosis of DD. However, numerous studies have highlighted frequent comorbidity between DD and Mood Disorders and have elucidated the importance of the affective state in the development and persistence of delusions. Thus, some factor analysis studies have identified the existence of a depressive dimension in DD, suggesting a substantial psychopathological heterogeneity in DD. However, these important affective features have not evaluated from a phenomenological point of view and in their relationship with delusions. Objectives The aim of the present study is to investigate the relationship between personality, trait affectivity and severity of delusions in patients with Delusional Disorder (DD). Methods Thirty-two outpatients affected by DD were administered the Structured Interview for DSM-IV-TR Personality Disorders (SIDP-IV), the Pathological Narcissism Inventory (NPI), the Positive and Negative Affect Schedule (PANAS) and the Psychotic Symptom Rating Scale (PSYRATS). Next, we analysed the prevalence of personality disorder in our sample of patients with DD and studied the correlations between the severity of delusions and the different affective variables. Finally, we obtained a multivariate explanatory model of the severity of the delusions. Results The severity of delusions was directly associated with “Grandiose Fantasy” item of narcissistic personality and inversely related with the feelings of shame, fear and guilt. In the multivariate model, the feeling of shame was the only independent variable capable of accounting for the severity of the delusions, that, in in DD patients, would lie on an affective core of shame.Table 2. Pearson correlation coefficient VARIABLES DRS total score GRANDIOSE FANTASY p = 0.045 SHAME p = 0.048 GUILT p = 0.016 AGITATION p = 0.049 FEAR p = 0.041 Table 3. Standardized coefficients in linear standard regression (DRS) DRS: total score R² β t p Step 1 0.157 - - - GRANDIOSE FANTASY - 0.396 1.89 0.048 Step 2 0.460 - - - GRANDIOSE FANTASY - 0.291 1.65 0.116 SHAME - -0.560 -3.17 0.005 Conclusions The severity of delusional beliefs in DD patients would lie on an affective core of shame upon predisposing personality traits. These findings could help to develop a psychotherapeutic approach for delusional patients focused in the feeling of shame. Disclosure of Interest None Declared

Abstract Background and Aim Steroids have long been used in inducing remission of inflammatory bowel disease (IBD). Chronic use, defined as therapy greater than 3 months, has been implicated in complications including increased hospital length of stay (LOS), infections, and even death. In our retrospective study, we aim to identify the complications of chronic steroid use in patients with IBD. Methods The fourth quarter of 2015–2019 National Inpatient Sample (NIS) was used in this study. International Classification of Diseases (ICD‐10) codes were used to identify patients with a diagnosis of IBD and chronic steroid use. Adverse outcomes of chronic steroid use in IBD patients were analyzed, such as osteoporosis, opportunistic infections, mortality rate, and LOS. Cohorts were weighted using an algorithm provided by the NIS allowing for accurate national estimates. Results A total of 283 970 patients had a diagnosis of IBD. Of those, 18 030 patients had concurrent chronic steroid use. Racial disparities existed, with 77.4% White, 12.7% Black, and 6.0% Hispanic. Patients with a history of IBD and chronic steroid use were found to have higher odds of developing osteoporosis, opportunistic infections, and acute thromboembolic events but did not have higher odds of mortality. Conclusion There is much controversy about whether IBD patients should be on chronic steroids for maintenance therapy and this study highlights the importance of this decision as patients on chronic steroid use had higher odds of developing adverse effects. These results stress the importance of monitoring patients on steroids and avoiding chronic use.

Background and Aims: We aimed to study the impact of acute myocardial infarction (AMI) in patients with celiac disease (CD). Methods: We used the National Inpatient Sample 2011–2018 to identify patients aged 18 years and older with a history of CD who presented with AMI using International Classification of Disease Nineth and Tenth Revision codes. Primary outcome of interest was mortality differences in AMI patients with and without CD. Secondary outcomes were in-hospital length of stay, hospital costs, and coronary revascularization. Results: A total of 2,287,840 weighted patients were included in this study with a principal diagnosis of AMI. Among this population, 183,027 weighted patients had a history of CD (0.08%), and 2,286,010 weighted patients had AMI without a history of CD (99.92%). Most AMI patients with and without CD were older (69.57 ± 13.21 vs 67.08 ± 13.87 years, respectively) and white (92.55% vs 75.39%, respectively). Patients with AMI and CD were more likely to be female than patients without CD (53.76% vs 38.47%; P < .05). In our study, we found that the difference in hospital charges (adjusted mean difference $2644.7) was lower among AMI and CD; however, length of stay was higher among patients with CD (adjusted mean difference 0.36 day) although they were not statistically significant (P > .05). Both cohorts had higher number of Medicare recipients and lower number of patients who self-pay. Our study also found that smoking was more prevalent among patients with CD, 12.14%, vs patients without CD, 2.51%. Moreover, patients with CD who developed AMI had a lower adjusted odds of mortality than those without CD (adjusted odds ratio [aOR] 0.41; P < .05). Patients with CD and AMI also had lower odds of coronary revascularization (aOR 0.80; P < .05). In addition, we found that adults with CD had a lower odds of developing AMI (aOR 0.78; P < .05). Conclusion: CD is a chronic disease leading to chronic inflammation and various nutrition-related problems which can lead to increased morbid conditions. However, we found lower odds of AMI among patients with CD, as well as lower mortality and comorbidities related to AMI, thus contradicting previous assumptions.

Hypertriglyceridemia is a well-established cause of acute pancreatitis. Initial treatment for hypertriglyceridemia-induced pancreatitis has consisted of supportive measures; however, triglyceride levels can remain high, causing prolonged organ failure and sepsis. Plasmapheresis has been proposed as a treatment option to effectively reduce triglyceride levels. We present a patient case of hypertriglyceridemia-induced pancreatitis that was treated with standard acute pancreatitis interventions along with plasmapheresis, after which triglyceride levels reduced significantly. Further research is necessary to determine the clinical benefits of plasmapheresis in treating this type of pancreatitis.

No meio rural, a água de consumo humano é frequentemente captada por meio de sistemas precários. O objetivo do trabalho foi o de monitorar parâmetros físicos, químicos e microbiológicos da qualidade de água subterrânea captada em fontes para uso doméstico, relacionando suas posições na paisagem e à presença de proteção física. Trinta e cinco fontes de água subterrânea, localizadas na pequena bacia hidrográfica-PBH do Arroio Lino, área rural do Município de Agudo - RS, foram amostradas e classificadas quanto à proteção física e à posição na paisagem. Monitoraram-se, de janeiro a agosto de 2002, os seguintes parâmetros da água: pH, cor, carbono orgânico solúvel total (COST), N-NO3, N-NH3 e fósforo total (PT), Escherichia coli e coliformes totais. Em geral, os parâmetros variaram com a época de coleta, ficando ora acima, ora abaixo dos Valores Máximos Permissíveis previstos pelo Ministério da Saúde do Brasil. A posição das fontes nas cotas mais altas da paisagem da PBH mostrou-se determinante unicamente para a cor e o PT. A proteção rudimentar mostrou-se eficaz para o PT nas fontes posicionadas em cotas altas, no entanto apresentou respostas discrepantes na parte baixa da paisagem, considerando-se os parâmetros COST e N-NO3. A fonte drenada coletiva, sistema recomendado pela assistência técnica oficial, mostrou-se a mais eficaz em evitar a contaminação por Escherichia coli, restringindo também coliformes totais, fósforo total e N-NO3 em relação à fonte individual. A posição das fontes na paisagem e a presença de proteção física rudimentar podem ser utilizadas como critério parcial ao uso de fontes para captação de água.In rural areas, water for human consumption is often captured by insecure systems. The objective of this work was monitoring some parameters of the quality of groundwater taken from sources, pointing out their position in the landscape and the presence of physical protection. For this , 36 sources in the watershed of Arroio Lino, a rural area of Agudo, RS, Brazil, were sampled and classified according their physical protection and position in the landscape. A monitoring program, from January to August 2002, was carried out to analyze the following parameters: pH, color, total soluble organic carbon - TSOC, N-NO3, N-NH3 and total phosphorus, E. coli and total coliforms. The parameters values changed with the time of collection and were often above the Maximum Allowable values provided by the Brazilian Ministry of Health. A rudimentary protection was efficient to the PT of the sources located in high levels; however it has present discrepant results for the low part of the landscape, considering the parameters TSOC e N-NO3. The collective drained source, system recommended by the official technical assistance, was the most efficient to avoid contamination by Escherichia coli, restricting also the levels of total coliforms, total phosphorus and N-NO3 as compared to the individual sources. The sources position in the landscape and the presence of a rudimentary physical protection can be employed as a partial criterion to accept that a water source be used for collecting water.

In this work the exposure of wells and surface water to pesticides, commonly used for tobacco cropping, was assessed. Water consumption wells and surface water flows were sampled at different times. After a preconcentration step with solid phase extraction (SPE), the selected pesticides were determined by gas chromatography with electron capture detection (GC-ECD) or high performance liquid chromatography with diode array detection (HPLC-DAD). No pesticides were detected in the well water samples and surface water flow in the winter season. However, in the spring and summer higher concentrations of chlorpyrifos and imidacloprid were found in the water source samples. Atrazine, simazine and clomazone were also found. The occurrence of pesticides in collected water samples was related with the application to tobacco.

We aim to study the impact of pulmonary hypertension on acutely exacerbated chronic obstructive pulmonary disease (AECOPD). We used the 2016 and 2017 National Readmission Database with an inclusion criterion of AECOPD as a primary and pulmonary hypertension as a secondary diagnosis using ICD 10‐CM codes. Exclusion criteria were age under 18 years, non‐elective admission, and discharge in December. The primary outcome was in‐hospital mortality during the index admission. Secondary outcomes were 30‐day readmission rate, resource utilization, and instrument utilization including intubation, prolonged invasive mechanical ventilation >96 h (PIMV), tracheostomy, chest tube placement, and bronchoscopy during the index admission. A total of 627,848 patients with AECOPD were included in the study, and 68,429 (10.90%) patients had a diagnosis of pulmonary hypertension. Pulmonary hypertension was more common among females (61.14%) with a mean age of 71 ± 11.66, Medicare recipients (79.5%), higher Charlson comorbidity index, and treatment in an urban teaching hospital. Pulmonary hypertension was associated with greater mortality (adjusted odds ratio (aOR) 1.89, p

Purpose: Adaptive MRgRT by 1.5 T MR-linac requires independent verification of the plan-of-the-day by the primary TPS (Monaco TM ) (M). Here we validated a Monte Carlo-based dose-check including the magnetostatic field, SciMoCa TM (S)., Methods: M and S were validated first in water, by comparison with commissioning-dosimetry. PDD(2x2cm 2 ) through a lung(air)-equivalent virtual-slab was then calculated. Clinical validation retrospectively included 161 SBRT plans, from five patients per-site: Pelvic-Nodes, Prostate, Liver, Pancreas, and Lungs. S-minus-M percentage differences (Δ%) were computed for target- and OARs-related dose-volume metrics. In-phantom dose verification per-patient was performed., Results: γ(2 %,1mm)-passing-rates (PR%) of in-water-computed PDD and transverse-dose-profiles vs. commissioning-dosimetry were (99.1 ± 2.0)% for M, and (99.3 ± 1.5)% for S. Calculated output-factors (OF) were typically within 1 % from measurements, except for OF(1x1cm 2 ) which was misestimated by -4.4 % and + 2.2 %, by M and S respectively. Dose spikes (valleys) on the PDD(2x2cm 2 ) by S across the lung-equivalent virtual-slab were slightly reduced with respect to M. In clinical plans, S computed higher V95% (p <0.05*, for pancreas and lung) and D2% (p <0.05*, for all sites) for the target, while D%>2% resulted for duodenal D(1cm 3 ), in Pancreas-SBRT, and for mean-lung-dose, in Lung-SBRT. All mostly due to the underestimated OF(1x1cm 2 ) by M. In-phantom dose verifications showed an average 1% increase in PR% by S vs. M., Conclusions: Beam-model quality in S resulted equivalent to M, thus making S useful both for an independent validation of the same beam-model in M, and for a daily validation of the M-based online approval decisions, without significantly delaying the clinical workflow (2-3 min)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Pellegrini serves as Director of Clinical Science at Elekta AB (Stockholm, Sweden). Prof. Alongi and Dr. Ruggieri received speaker honoraria from Elekta AB. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article., (Copyright © 2025 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objective: This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT)., Materials and Methods: Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software., Results: In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5 Gy; for patients with subclinical heart damage, the mean MHD was 1.6 Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage., Conclusion: Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events., Competing Interests: Declarations. Conflict of interest: Icro Meattini declares occasional small fees received for advisory boards supported by Eli Lilly, Novartis, Astra Zeneca, Daiichi Sankyo, Gilead, SeaGen, Pfizer, and Menarini StemLine. Roberto Pellegrini is an employee of Elekta AB (Stockholm, Sweden). Isacco Desideri, Jacopo Nori, and Lorenzo Livi are editors in this journal. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Florence. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication., (© 2024. Italian Society of Medical Radiology.)

Background: Janus kinase inhibitors (JAKis) are a novel class of drugs interfering with intracellular signaling of type I and type II cytokines, which play a crucial role in immune dysregulation associated with several chronic inflammatory diseases. Filgotinib (FIL), in particular, is the newest member of the JAKi class and exerts its therapeutic effects by selectively targeting and inhibiting the kinase activity of JAK1. While the efficacy of FIL in rheumatoid arthritis (RA) has been confirmed in clinical trials, real-world evidence may provide better insights into its effectiveness and safety in routine clinical practice. Methods: We performed a multicenter, retrospective cohort study investigating the real-life effectiveness and safety of FIL in adult patients with RA. Demographic information, disease characteristics, prior treatment history, and comorbid conditions were retrieved from clinical records at baseline (M0) and after 3 (M3) and 6 months (M6) of treatment. Results: A total of 82 patients (63 women) agreed to participate in the study, of whom 39 (47.6%) were older than 65 years. The average RA duration was 13 ± 9 years; 19 patients (23.1%) were current or former smokers, and 4 patients (4.9%) had a history of cardiovascular events. Most patients had previously received at least one biologic disease-modifying antirheumatic drug (range: 1-6+); in addition, 11 patients (13.4%) had been already exposed to another JAKi. During the follow-up, 7 patients discontinued treatment due to primary failure ( n = 3) or adverse events ( n = 4). Significant reductions in pain and number of tender and swollen joints were observed at M3 and M6. A relevant proportion of patients achieved DAS28-CRP remission at M3 and M6 (46.3% and 66.2%, respectively). Conclusions: Our data provide additional insight into the effectiveness of filgotinib in a real-world setting, even among patients with difficult-to-treat RA and a high prevalence of cardiovascular risk factors.

Objective: To assess adverse obstetric and neonatal outcomes associated with the use of dinoprostone for induction of labor, with particular attention on categories for which caution is recommended by the Italian Medicines Agency and the European Medicine Agency., Methods: A retrospective multicenter observational study was conducted on a population of 1687 patients undergoing induction of labor with vaginal dinoprostone (gel or insert) between August 2019 and June 2022. Patients were subdivided based on maternal age, gestational age, and obstetric disorders. Data regarding the mode of delivery, the incidence of tachysystole, and the obstetric and perinatal outcomes were collected., Results: The main adverse event associated with the use of dinoprostone was tachysystole. However, tachysystole was not associated with an increased risk of cesarean section (CS), neonatal intensive care (NICU) admission, low 1-min Apgar, or umbilical cord acidosis. Maternal age greater than 35 years, gestational age greater than 40 weeks, and obstetric disorders were not associated with an increased rate of tachysystole, NICU admission, low 1- and 5-min Apgar scores, and cord acidosis. The only associated adverse outcomes in those categories were postpartum hemorrhage with age greater than 35 years and tachysystole with gestational diabetes mellitus and hypertensive disorders. Not a single case of severe outcome (disseminated intravascular coagulation, uterine rupture, maternal and fetal death) was reported in the cohort., Conclusion: Providing there is adequate maternal and fetal surveillance, in an inpatient setting, dinoprostone could be safely administered for the induction of labor and considered appropriate in high-risk pregnancies. Tachysystole can be self-identified by the patient and effectively managed., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

An interplay between Pd and PdO and their spatial distribution inside the particles are relevant for numerous catalytic reactions. Using in situ time-resolved X-ray absorption spectroscopy (XAS) supported by theoretical simulations, a mechanistic picture of the structural evolution of 2.3 nm palladium nanoparticles upon their exposure to molecular oxygen is provided. XAS analysis revealed the restructuring of the fcc-like palladium surface into the 4-coordinated structure of palladium oxide upon absorption of oxygen from the gas phase and formation of core@shell Pd@PdO structures. The reconstruction starts from the low-coordinated sites at the edges of palladium nanoparticles. Formation of the PdO shell does not affect the average Pd‒Pd coordination numbers, since the decrease of the size of the metallic core is compensated by a more spherical shape of the oxidized nanoparticles due to a weaker interaction with the support. The metallic core is preserved below 200 °C even after continuous exposure to oxygen, with its size decreasing insignificantly upon increasing the temperature, while above 200 °C, bulk oxidation proceeds. The Pd‒Pd distances in the metallic phase progressively decrease upon increasing the fraction of the Pd oxide due to the alignment of the cell parameters of the two phases., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Artificial intelligence can standardize and automatize highly demanding procedures, such as manual segmentation, especially in an anatomical site as common as the pelvis. This study investigated four automated segmentation tools on computed tomography (CT) images in female and male pelvic radiotherapy (RT) starting from simpler and well-known atlas-based methods to the most recent neural networks-based algorithms. The evaluation included quantitative, qualitative and time efficiency assessments. A mono-institutional consecutive series of 40 cervical cancer and 40 prostate cancer structure sets were retrospectively selected. After a preparatory phase, the remaining 20 testing sets per each site were auto-segmented by the atlas-based model STAPLE, a Random Forest-based model, and two Deep Learning-based tools (DL), MVision and LimbusAI. Setting manual segmentation as the Ground Truth, 200 structure sets were compared in terms of Dice Similarity Coefficient (DSC), Hausdorff Distance (HD), and Distance-to-Agreement Portion (DAP). Automated segmentation and manual correction durations were recorded. Expert clinicians performed a qualitative evaluation. In cervical cancer CTs, DL outperformed the other tools with higher quantitative metrics, qualitative scores, and shorter correction times. On the other hand, in prostate cancer CTs, the performance across all the analyzed tools was comparable in terms of both quantitative and qualitative metrics. Such discrepancy in performance outcome could be explained by the wide range of anatomical variability in cervical cancer with respect to the strict bladder and rectum filling preparation in prostate Stereotactic Body Radiation Therapy (SBRT). Decreasing segmentation times can reduce the burden of pelvic radiation therapy routine in an automated workflow., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death., Methods: Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6-29) and 28-day all-cause mortality (Days 1-29)., Results: One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 10 9 /L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: -4.46, 34.78; P = 0.096)., Conclusion: Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728., (© 2024. The Author(s).)

Aim: To validate a fully-automated lexicographic optimization-planning system (mCycle, Elekta) for single-(SL) and multiple-(ML, up to 4 metastases) lesions in intracranial stereotactic radiosurgery (SRS, 21 Gy, single fraction)., Methods: A pre-determined priority list, Wish-List (WL), represents a dialogue between planner and clinician, establishing strict constraints and pursuing objectives. In order to satisfy the clinical protocol without manual intervention, four patients were required to tweak and fine-tune each WL (SLp, MLp) for coplanar arcs. Thirty-five testing plans (20 SLp, 15 MLp) were automatically re-planned (mCP). Automatic and manual plans were compared including dose constraints, conformality, modulation complexity score (MCS), delivery time, and local gamma analysis (2%/2 mm). To ensure plan clinical acceptability, two radiation oncologists conducted an independent blind plan choice., Results: Each WL-tuning took 3 days. Estimated median manual plans and mCP calculation time were 8 and 3 h, respectively. Significant increases in SLp and MLp target coverage and conformity were registered. mCP showed a not significant and clinically acceptable higher median brain V 12 Gy . SLp registered a -5.8% MU decrease with comparable median delivery time (MP 2.0 min, mCP 1.9 min) while MLp showed a +9.8% MU increase and longer delivery time (MP 3.5 min, mCP 4.4 min). mCP MCS resulted significantly higher without affecting gamma passing rates. At blind choice, mCP were preferred in the majority of cases., Conclusions: Lexicographic optimization produced acceptable SRS plans with coplanar arcs significantly reducing the overall planning time in cases with up to 4 brain metastases. These planning improvements suggest further investigations by setting high-quality non-coplanar arc plans as a reference., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Patients with endometriosis are thought to have been impacted by the COVID-19 pandemic and estimates suggest that 6.2% of them were infected with SARS-CoV-2., Methods: This is a retrospective cohort study enrolling 284 women at the Polyclinic of Modena between January 2020 and April 2021. Patients were given specific questionnaires to investigate COVID-19 infection and any changes in gynecological symptoms. All patients were also administered the Hospital Anxiety and Depression Syndrome (HADS) Questionnaire to assess the psychological impact of the COVID-19 pandemic. The primary outcome was to assess the clinical impact and any worsening of gynecological symptoms after COVID-19 infection; the secondary outcome was to evaluate the clinical and psychological impact of the COVID-19 pandemic in patients with endometriosis or chronic pelvic pain., Results: A total of 170 women experienced COVID-19 infection, while 114 were consistently negative and asymptomatic for COVID-19. The two groups showed similar baseline. A total of 122 women with COVID-19 infection and 106 COVID-19 negative patients had already the vaccine administration with two doses of vaccine (72.20% vs. 93%, P=0.001). Among the 170 patients affected by COVID-19, 41 (24%) reported worsening gynecologic endometriosis symptoms, during the infection. According to our results, 196 of 284 reported changes in their gynecological health status during pandemic, and 84 reported symptomatic worsening (42.9%); 24% of patients with infection reported feeling slowed down vs. 15.8% of unaffected patients (P=0.065) and 44% of positive patients reported loss of interest in self-care vs. 31% of negative patients (P=0.055)., Conclusions: Patients with endometriosis seemed to have worsening gynecological and psychological clinical status during the pandemic.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose ( p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD ( p = 0.005, p ≤ 0.001) and mean LAD dose ( p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Background: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans., Methods: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB). The Planning Target Volume (PTV) was obtained by applying a 5 mm isotropic expansion to the CTV (Clinical Target Volume), with a 5 mm clip from the skin. Comparisons of dosimetric parameters and delivery/planning times were conducted. Dosimetric verification of the AP-VMAT plans was performed., Results: The study showed statistically significant improvements in AP-VMAT plans compared to HT for OARs (Organs At Risk) mean dose, except for the heart and ipsilateral lung. No significant differences in V 95% were observed for PTV breast/CW and PTV III-IV, while increased coverage (higher V 95% ) was seen for PTV IMN in AP-VMAT plans. HT plans exhibited smaller values of PTV V 105% for breast/CW and III-IV, with no differences in PTV IMN and boost. HT had an average (± standard deviation) delivery time of (17 ± 8) minutes, while AP-VMAT took (3 ± 1) minutes. The average γ passing rate for AP-VMAT plans was 97%±1%. Planning times reduced from an average of 6 h for HT to about 2 min for AP-VMAT., Conclusions: Comparing AP-VMAT plans with clinical HT plans showed similar or improved quality. The implementation of mCycle demonstrated successful automation of the planning process for VMAT treatment of locally advanced breast cancer, significantly reducing workload., (© 2023. The Author(s).)

During the early stage of the COVID-19 pandemic (winter 2020), the northern part of Italy has been significantly affected by viral infection compared to the rest of the country leading the scientific community to hypothesize that airborne particulate matter (PM) could act as a carrier for the SARS-CoV-2. To address this controversial issue, we first verified and demonstrated the presence of SARS-CoV-2 RNA genome on PM 2.5 samples, collected in the city of Bologna (Northern Italy) in winter 2021. Then, we employed classical molecular dynamics (MD) simulations to investigate the possible recognition mechanism(s) between a newly modelled PM 2.5 fragment and the SARS-CoV-2 Spike protein. The potential molecular interaction highlighted by MD simulations suggests that the glycans covering the upper Spike protein regions would mediate the direct contact with the PM 2.5 carbon core surface, while a cloud of organic and inorganic PM 2.5 components surround the glycoprotein with a network of non-bonded interactions resulting in up to 4769 total contacts. Moreover, a binding free energy of -207.2 ± 3.9 kcal/mol was calculated for the PM-Spike interface through the MM/GBSA method, and structural analyses also suggested that PM attachment does not alter the protein conformational dynamics. Although the association between the PM and SARS-CoV-2 appears plausible, this simulation does not assess whether these established interactions are sufficiently stable to carry the virus in the atmosphere, or whether the virion retains its infectiousness after the transport. While these key aspects should be verified by further experimental analyses, for the first time, this pioneering study gains insights into the molecular interactions between PM and SARS-CoV-2 Spike protein and will support further research aiming at clarifying the possible relationship between PM abundance and the airborne diffusion of viruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic., Patients and Method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines., Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients ( death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001)., Conclusions: An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients' population., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Alessandro Antonelli reports financial support was provided by Italian 10.13039/100009647Ministry of Health, Ricerca Finalizzata (RF-2021-12374986) Destinatario istituzionale: Regione Toscana. Unità Operative:U.O.1: Azienda Ospedaliero-Universitaria Pisana; U.O.2: Azienda Ospedaliero-Universitaria Aldo Moro Bari; U.O.3: Azienda Ospedaliero-Universitaria Modena, CUP Master: D55E22000670001., (© 2023 Published by Elsevier B.V.)

Background: To investigate the capability of a not-yet commercially available fully automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), to further improve the plan quality of an already-validated Wish List (WL) pushing on the organs-at-risk (OAR) sparing without compromising target coverage and plan delivery accuracy., Material and Methods: Twenty-four mono-institutional consecutive cervical cancer Volumetric-Modulated Arc Therapy (VMAT) plans delivered between November 2019 and April 2022 (50 Gy/25 fractions) have been retrospectively selected. In mCycle the LO planning algorithm was combined with the a-priori multi-criterial optimization (MCO). Two versions of WL have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). Robust WLs have been tuned using a subset of 4 randomly selected patients. The remaining plans have been automatically re-planned by using the designed WLs. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, ranking the three competing plans. Furthermore, a previous defined global quality index has been used to gather into a single score the plan quality evaluation., Results: The WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took in both cases 3 working days. mCP01 best performed in terms of target coverage (PTV V 95% (%): MP 98.0 [95.6-99.3], mCP01 99.2 [89.7-99.9], mCP02 96.9 [89.4-99.5]), while mCP02 showed a large OAR sparing improvement, especially in the rectum parameters (e.g., Rectum D 50% (Gy): MP 41.7 [30.2-47.0], mCP01 40.3 [31.4-45.8], mCP02 32.6 [26.9-42.6]). An increase in plan complexity has been registered in mCPs without affecting plan delivery accuracy. In the blind comparisons, all automated plans were considered clinically acceptable, and mCPs were preferred over MP in 90% of cases. Globally, automated plans registered a plan quality score at least comparable to MP., Conclusions: This study showed the flexibility of the Lexicographic approach in creating more demanding Wish Lists able to potentially minimize toxicities in RT plans., (© 2023. Springer Science+Business Media, LLC.)

Objectives: To better define the spectrum of new-onset post-COVID-19 and post-COVID-19 vaccine inflammatory rheumatic diseases (IRD) from a large multicentric observational study., Methods: Consecutive cases of IRD encountered during a 12-month period and satisfying one of the following inclusion criteria: (a) onset of the rheumatic manifestations within 4 weeks from SARS-CoV-2 infection or (b) onset of the rheumatic manifestations within 4 weeks from the administration of one of the COVID-19 vaccines ws recruited., Results: The final analysis cohort comprised 267 patients, of which 122 (45.2%) in the post-COVID-19 and 145 (54.8%) in the postvaccine cohort. Distribution of IRD categories differed between the two cohorts: the post-COVID-19 cohort had a higher percentage of patients classified as having inflammatory joint diseases (IJD, 52.5% vs 37.2%, p=0.013) while the post-vaccine cohort had a higher prevalence of patients classified as polymyalgia rheumatica (PMR, 33.1% vs 21.3%, p=0.032). No differences were detected in the percentage of patients diagnosed with connective tissue diseases (CTD 19.7% vs 20.7%, p=0.837) or vasculitis (6.6% vs 9.0%, p=0.467). Despite the short follow-up period, IJD and PMR patients' response to first-line therapy was favourable, with both groups achieving a drop in baseline disease activity scores of ~30% and ~70% respectively., Conclusion: Our article reports the largest cohort published to date of new-onset IRD following SARS-CoV-2 infection or COVID-19 vaccines. Although causality cannot be ascertained, the spectrum of possible clinical manifestations is broad and includes IJD, PMR, CTD and vasculitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Budd-Chiari syndrome is a rare disorder characterized by obstruction of hepatic venous outflow involving either the hepatic veins or the inferior vena cava. Risk factors include thrombophilia and myeloproliferative disorders, and symptoms are often unspecific. We present a case of a 60-year-old woman admitted to our medical unit for ascites and abdominal pain. Although her medical history significant for a mixed connective tissue disease and a mild increase of the transaminases had raised the suspicion of autoimmune hepatitis, the demonstration on computed tomography of the absence of outflow in the terminal tract of the supra-hepatic veins allowed a correct diagnosis. The contribution of radiological imaging is fundamental in the diagnosis of this rare and elusive pathology., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Introduction: Pressure and shear stresses applied to the stump of a transfemoral amputee wearing a newly designed prosthetic socket have been analyzed by a finite element modeling approach., Methods: The new socket was developed by the Istituto Tecnico Ortopedico Preneste, and it was named the "hybrid subischial socket." This work aimed at understanding the loads' distribution on the stump surface in 2 operative conditions: at the end of the wearing phase and during the orthostatic posture. The model of the stump was composed of 4 different materials: the femoral bone, the muscle tissue, the fat, and the skin layers. Except for the bone (rigid), the biological tissues were modeled as Neo-Hookean, and their mechanical properties were taken from the literature. The socket was composed of a containment frame, made of carbon fiber composite material, a shell made of flexible silicone, and a liner made of hyperelastic silicone., Results: The results of our simulation show that the main support areas are located in a proper position, in agreement with the ideal principles of this prosthetic design, and the maximum pressures are well below the pain threshold reported in the literature for the same contact areas., Conclusions: We can conclude that although the upper rim of the socket is well below the ischiatic area, the new socket design allows for a safe and comfortable support of the body weight. This is in agreement with the evidence of a good functionality and acceptance of this prosthetics gathered in the many real applications., (Copyright © 2023 International Society for Prosthetics and Orthotics.)

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were -3.0% [-18.5-2.8] for CTV D99% and -2.6% [-17.8-1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments., Competing Interests: The authors declare no conflict of interest.

Aim: In this study, a not yet commercially available fully-automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), was validated for cervical cancer., Material and Methods: Twenty-four mono-institutional consecutive treatment plans (50 Gy/25 fx) delivered between November 2019 and April 2022 were retrospectively selected. The automatic re-planning was performed by mCycle, implemented in the Monaco TPS research version (v5.59.13), in which the LO and Multicriterial Optimization (MCO) are coupled with Monte Carlo calculation. mCycle optimization follows an a priori assigned priority list, the so-called Wish List (WL), representing a dialogue between the radiation oncologist and the planner, setting hard constraints and following objectives. The WL was tuned on a patient subset according to the institution's clinical protocol to obtain an optimal plan in a single optimization. This robust WL was then used to automatically re-plan the remaining patients. Manual plans (MP) and mCycle plans (mCP) were compared in terms of dose distributions, complexity (modulation complexity score, MCS), and delivery accuracy (perpendicular diode matrices, gamma analysis-passing ratio, PR). Their clinical acceptability was assessed through the blind choice of two radiation oncologists. Finally, a global quality score index (SI) was defined to gather into a single number the plan evaluation process., Results: The WL tuning requested four patients. The 20 automated re-planning tasks took three working days. The median optimization and calculation time can be estimated at 4 h and just over 1 h per MP and mCP, respectively. The dose comparison showed a comparable organ-at-risk spare. The planning target volume coverage increased (V 95% : MP 98.0% [95.6-99.3]; mCP 99.2%[89.7-99.9], p >0.05). A significant increase has been registered in MCS (MP 0.29 [0.24-0.34]; mCP 0.26 [0.23-0.30], p <0.05) without affecting delivery accuracy (PR (3%/3mm): MP 97.0% [92.7-99.2]; mCP 97.1% [95.0-98.6], p >0.05). In the blind choice, all mCP results were clinically acceptable and chosen over MP in more than 75% of cases. The median SI score was 0.69 [0.41-0.84] and 0.73 [0.51-0.82] for MP and mCP, respectively (p >0.05)., Conclusions: mCycle plans were comparable to clinical manual plans, more complex but accurately deliverable and registering a similar SI. Automated plans outperformed manual plans in blinded clinical choice., Competing Interests: RP serves as Director of Clinical Science at Elekta AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trivellato, Caricato, Pellegrini, Montanari, Daniotti, Bordigoni, Faccenda, Panizza, Meregalli, Bonetto, Arcangeli and De Ponti.)

As COVID-19 has spread worldwide, conspiracy theories have proliferated rapidly on social media platforms, adversely affecting public health. For this reason, media literacy interventions have been highly recommended, although the impact of critical social media use on the development of COVID-19 conspiracy theories has not yet been empirically studied. Moreover, emotional dysregulation may play another crucial role in the development of such theories, as they are often associated with stress, anxiety, lack of control, and other negative emotions. Therefore, the aim of this study was to test the hypothesis that emotion dysregulation would be positively associated with conspiracy beliefs about COVID-19 and that critical use of social media would attenuate this association. Data from 930 Italian participants (339 men and 591 women) were collected online during the third wave of the COVID-19 outbreak. A moderated model was tested using the PROCESS Macro for SPSS. Results showed that: (1) emotion dysregulation and critical social media use accounted for a significant proportion of the variance in conspiracy beliefs about COVID-19; and (2) critical social media use moderated the effect of emotion dysregulation on conspiracy beliefs about COVID-19. Implications for preventing the spread of conspiracy theories are discussed.

Autoimmune systemic diseases (ASD) show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed at evaluating the seroconversion elicited by COVID-19 vaccine over the entire vaccination cycle including the booster dose. Among 478 unselected ASD patients originally evaluated at the end of the first vaccination cycle (time 1), 344 individuals were re-evaluated after a 6-month period (time 2), and 244 after the booster vaccine dose (time 3). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was assessed by measuring serum IgG-neutralizing antibody (NAb) on samples obtained at the three time points in both patients and 502 age-matched controls. In the 244 ASD group that received booster vaccine and monitored over the entire follow-up, the mean serum NAb levels (time 1, 2, and 3: 696.8 ± 52.68, 370.8 ± 41.92, and 1527 ± 74.16SD BAU/mL, respectively; p < 0.0001) were constantly lower compared to controls (p < 0.0001), but they significantly increased after the booster dose compared to the first two measurements (p < 0.0001). The percentage of patients with absent/suboptimal response to vaccine significantly decreased after the booster dose compared to the first and second evaluations (time 1, 2, and 3: from 28.2% to 46.3%, and to 7.8%, respectively; p < 0.0001). Of note, the percentage of patients with absent/suboptimal response after the booster dose was significantly higher compared to controls (19/244, 7.8% vs 1/502, 0.2%; p < 0.0001). Similarly, treatment with immune-modifiers increased the percentage of patients exhibiting absent/suboptimal response (16/122, 13.1% vs 3/122, 2.46%; p = 0.0031). Overall, the above findings indicate the usefulness of booster vaccine administration in ASD patients. Moreover, the persistence of a significantly higher percentage of individuals without effective seroconversion (7.8%), even after the booster dose, warrants for careful monitoring of NAb levels in all ASD patients to identify those with increased risk of infection. In this particularly frail patients' setting, tailored vaccination and/or therapeutic strategy are highly advisable., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The present work deals with a scintillation detector made of a LuYAP:Ce array coupled to a position-sensitive photo-multiplier tube, whose structure is well suitable for SPECT and PET, but also in nuclear physics, astrophysics, astroparticle physics, homeland security, and non-proliferation. The response was investigated under Co-57, Ba-133, Cs-137 gamma-ray irradiation, and with Lu-176 self-activity. The investigation, based on the 2-D charge-profiles spread, provides means for identifying and rejecting multiple-interactions in the crystal-array, like Lu X-ray escape photons, and Compton-scattered ones., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Adaptive stereotactic body radiation therapy (SBRT) for prostate cancer (PC) by the 1.5 T MR-linac currently requires online planning by an expert user. A fully automated and user-independent solution to adaptive planning (mCycle) of PC-SBRT was compared with user's plans for the 1.5 T MR-linac., Methods and Materials: Fifty adapted plans on daily magnetic resonance imaging scans for 10 patients with PC treated by 35 Gy (prescription dose [D p ]) in 5 fractions were reoptimized offline from scratch, both by an expert planner (manual) and by mCycle. Manual plans consisted of multicriterial optimization (MCO) of the fluence map plus manual tweaking in segmentation, whereas in mCycle plans, the objectives were sequentially optimized by MCO according to an a-priori assigned priority list. The main criteria for planning approval were a dose ≥95% of the D p to at least 95% of the planning target volume (PTV), V 33.2 (PTV) ≥ 95%, a dose less than the D p to the hottest cubic centimeter (V 35 ≤ 1 cm 3 ) of rectum, bladder, penile bulb, and urethral planning risk volume (ie, urethra plus 3 mm isotropically), and V 32 ≤ 5%, V 28 ≤ 10%, and V 18 ≤ 35% to the rectum. Such dose-volume metrics, plus some efficiency and deliverability metrics, were used for the comparison of mCycle versus manual plans., Results: mCycle plans improved target dose coverage, with V 33.2 (PTV) passing on average (±1 SD) from 95.7% (±1.0%) for manual plans to 97.5% (±1.3%) for mCycle plans ( P < .001), and rectal dose sparing, with significantly reduced V 32 , V 28 , and V 18 ( P ≤ .004). Although at an equivalent number of segments, mCycle plans consumed moderately more monitor units (+17%) and delivery time (+9%) ( P < .001), whereas they were generally faster (-19%) in terms of optimization times ( P < .019). No significant differences were found for the passing rates of locally normalized γ (3 mm, 3%) ( P  = .059) and γ (2 mm, 2%) ( P  = .432) deliverability metrics., Conclusions: In the offline setting, mCycle proved to be a trustable solution for automated planning of PC-SBRT on the 1.5 T MR-linac. mCycle integration in the online workflow will free the user from the challenging online-optimization task., (© 2021 The Author(s).)

Objective: Autoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients., Methods: The study included 3,918 ASD pts (815 M, 3103 F; mean age 59±12SD years) consecutively recruited between March 2020 and May 2021 at the 36 referral centers of COVID-19 and ASD Italian Study Group. The possible development of COVID-19 was recorded by means of a telephone survey using a standardized symptom assessment questionnaire., Results: ASD patients showed a significantly higher prevalence of COVID-19 (8.37% vs. 6.49%; p<0.0001) but a death rate statistically comparable to the Italian general population (3.65% vs. 2.95%). Among the 328 ASD patients developing COVID-19, 17% needed hospitalization, while mild-moderate manifestations were observed in 83% of cases. Moreover, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular events; systemic sclerosis (SSc) patients showed a significantly higher COVID-19-related death rate compared to the general population (6.29% vs. 2.95%; p=0.018). Major adverse prognostic factors to develop COVID-19 were: older age, male gender, SSc, pre-existing ASD-related interstitial lung involvement, and long-term steroid treatment. Of note, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs. 46.99%; p=0.000), as well as the SSc patients treated with low dose aspirin (with 5.57% vs. without 27.84%; p=0.000)., Conclusion: During the first three pandemic waves, ASD patients showed a death rate comparable to the general population despite the significantly higher prevalence of COVID-19. A significantly increased COVID-19- related mortality was recorded in only SSc patients' subgroup, possibly favored by preexisting lung fibrosis. Moreover, ongoing long-term treatment with csDMARDs in ASD might usefully contribute to the generally positive outcomes of this frail patients' population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Fourteen asymptomatic normocephalic newborns with confirmed congenital Zika infection were investigated. All newborns presented Zika virus (ZIKV) positivity on reverse transcriptase polymerase chain reaction. Following ZIKV-specific NS5 gene fragment sequencing in one child, phylogenetic analysis revealed that this isolate belonged to the Asian genotype, and clustered closely with other sequences previously isolated in north-east and northern regions of Brazil., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to evaluate the possible relationship between cultural specimens and preterm birth in women admitted for threatened preterm labor. Preterm birth is the leading cause of neonatal mortality and antenatal hospitalization; several risk factors including intrauterine infections have been identified, but its real causes remain poorly understood., Design: This is a retrospective, multicenter, cohort study including 250 women admitted for threatened preterm labor. Methods, Participants/Materials, Setting: All women admitted for threatened preterm labor, i.e., presenting with cervical changes and uterine activity before 37 weeks at the obstetrics unit of the hospitals of Modena, Monza, Carate, and Vimercate were included in the study. We excluded twin pregnancies and cases with preterm premature rupture of membranes at admission. Data about maternal history, pregnancy complications, cervical length, vaginal swabs, and urine culture at admission and gestational age at delivery were collected from clinical records in order to compare the incidence of preterm birth according to some known risk factors, cervical length, and microbiological test at admission., Results: 250 women were included in the study; preterm birth at less than 37 weeks occurred in 44.4% women admitted for threatened preterm labor. The incidence of preterm birth was not different between those with a positive or a negative vaginal swab (48.3 vs. 38.4%, p = 0.22) or positive versus negative urine culture (31.8 vs. 42.1%, p = 0.23) at admission. A shorter cervical length at admission was found in women with subsequent preterm birth (17 vs. 19.5 mm, p = 0.03). Cervical length <15 mm (OR 1.82, 95% CI: 1.03-3.23, p = 0.039) predicted the risk of preterm birth. Furthermore, only the history of a previous preterm birth (p = 0.02) and a previous uterine curettage (p = 0.045) was associated with preterm birth., Limitations: The observational and retrospective nature of the study and its small sample size are important limitations of the study. Moreover, women were not systematically or randomly assigned to the screening for vaginal or urinary infections., Conclusions: There is no evidence that the search for vaginal or urinary infections in women admitted for threatened preterm labor is helpful to identify those at increased risk of preterm birth. Although several studies have explored the role of screening for bacterial vaginosis in asymptomatic women and some studies evaluated vaginal or urinary infections in women with preterm birth, none of them focused on the possible role of microbiological specimens as a predictive tool in women admitted for threatened PTL. No association was found in our study, but prospective randomized controlled trials are required to confirm the results of this observation., (© 2022 S. Karger AG, Basel.)

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53-1203) vs 825 (451-1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The subischial socket interface design is a promising new shape of socket for persons with transfemoral amputation. Typically, the proximal trim line is located distal to the ischial tuberosity, improving comfort in prosthetic users without interfering with gait parameters compared to Ischial Containment Socket (ICS). No studies have investigated the performances of a subischial sockets with suction suspension system. A new subischial socket (Hybrid Subischial Socket - HySS) combined with a hypobaric passive suspension system has been recently developed., Objective: To assess the effects of HySS in terms of comfort, hip range-of-motion and gait parameters., Methodology: Three persons with transfemoral amputation were tested first using their usual ICS and then after one month of continuous use of HySS., Findings: The following parameters improved in all participants using HySS: 1) hip range-of-motion, 2) walking speed and distance, 3) Timed-Up-and-Go-Test time, 4) stride length, 5) double support duration, 6) peak value of hip extension during stance, 7) satisfaction with the prosthesis., Conclusion: These findings suggest that the use of HySS could allow improvements for prosthetic use., Competing Interests: All the authors declare to have no conflicts of interest to declare., (Copyright (c) 2021 Pellegrini R, Denza G, Brunelli S, Zenardi D, Imperio M, Vannozzi G, Traballesi M.)

Introduction: Nursing theories are essential for orienting nursing practice. To date, three models for nursing practice have been developed in Italy. In addition, significant epistemological reflections have been published, sparking a rich professional debate regarding the theoretical foundations of nursing in Italy. However, conceptual models from other countries are often still used, despite many difficulties associated with applying them in practice. In order to investigate and redress this 'theoretical gap' and related implications for intervention, three scoping reviews of the Italian nursing literature were conducted to examine three categories of nursing knowledge: (a) nursing practice in Italy; (b) the basic nursing concepts of person, health, environment and nursing; and (c) regulatory/normative statements regarding what nursing practice should be in Italy., Aim: The purpose of this investigation was to identify how nursing is conceptualized in the Italian literature through an integrative narrative analysis of three scoping reviews., Methods: The Scoping Review according to the recommendations published by Arksey and O'Malley and subsequently implemented by Levac et al. has been selected as the optimal methodology for mapping nursing knowledge. At the end of the reviews carried out to answer the three research questions, the researchers integrated the results by conducting a coding of the results., Results: The narrative synthesis highlighted a systemic conception of persons in their social context, 'incorporated' within relational systems. Persons are imagined as active agents with self-determination toward promoting their own health. Health, derived from levels of equilibrium between multiple systemic components and based on the person's holistic view, is a fundamental right and a collective social interest. Maintaining or promoting a person's health requires careful consideration of all these constitutive and integral elements. The nursing process is implemented through technical acts as well as relational and caring skills. Professional autonomy, influenced by clinical and organizational contexts, is expressed in collaboration with other professionals who contribute to the healthcare process. The results of this integrative narrative analysis suggest the need for a holistic vision of persons, with an active role in their health management, indissociable from the system of relationships in which this is contextualized, within which nurses are embedded., Conclusion: In light of the results of our investigation, the promotion of a conceptualization of nursing based on the centrality of the person-social relational system and on the active role of persons that nurses work with, this could guide approaches used in nursing education and administration. This could help enhance care provided by nurses and persons' participation in decisions regarding their own health.

Introduction: Cancer is the second leading cause of death in the world, and it is expected to be the main cause by the year 2030. Current trends of higher incidence and the introduction of new treatments lead to the challenge of treating more people with increasing costs per capita. In Brazil, current and future challenges are even more significant because of the limited resources destined for healthcare., Methods: We propose a methodology to compare cost-effectiveness performance with a regression of cancer lethality against the resources available for different nations, using the gross domestic product and the mortality-to-incidence ratio. Our objective is to evaluate and compare outcomes observed in Brazil., Results: According to our methodology, Brazil is performing well in breast and prostate cancer (observed lethality 9% and 15% lower than expected, respectively). It performs close to expected in colon (0.8% higher) and cervix (2% higher). However, lung cancer had a higher lethality than expected (6.5% higher). We also found that breast, prostate and cervical cancers are the primary sites more related to income. Lung cancer had the weakest relationship with resources., Conclusion: Brazil has different cost-effectiveness results in the management of cancer depending on the primary site. Also, national income has a significant and heterogeneous effect on the lethality of different tumour types. This economic analysis is important for low- to middle-income countries seeking to evaluate cancer outcomes in limited-resource settings., Competing Interests: Rodrigo Pellegrini: NoneTomás Reinert: Speaker honoraria: Novartis, AstraZeneca, Pfizer, Libbs, Lilly, Pierre FabreConsulting or advisory role: AstraZeneca, Lilly, NovartisResearch funding: AstraZenecaCarlos Henrique Barrios: Stock and other ownership interests: Biomarker, MedSIR, TummiSpeaker honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, EisaiConsulting or advisory role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Libbs, MSD Oncology, United MedicalResearch funding: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, Biomarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis BioScience, AB Science, Asana Biosciences, Medivation, Exelixis, ImClone Systems, LEO Pharma, Millennium, Janssen, Atlantis Clinica, INC Research, Halozyme, Covance, Celgene, inVentiv HealthTravel, accommodations, expenses: Roche/Genentech, Novartis, Pfizer, BMS Brazil, AstraZeneca, MSD Oncology, (© the authors; licensee ecancermedicalscience.)

Palladium-based catalysts are exploited on an industrial scale for the selective hydrogenation of hydrocarbons. The formation of palladium carbide and hydride phases under reaction conditions changes the catalytic properties of the material, which points to the importance of operando characterization for determining the relation between the relative fractions of the two phases and the catalyst performance. We present a combined time-resolved characterization by X-ray absorption spectroscopy (in both near-edge and extended regions) and X-ray diffraction of a working palladium-based catalyst during the hydrogenation of ethylene in a wide range of partial pressures of ethylene and hydrogen. Synergistic coupling of multiple techniques allowed us to follow the structural evolution of the palladium lattice as well as the transitions between the metallic, hydride and carbide phases of palladium. The nanometric dimensions of the particles resulted in the considerable contribution of both surface and bulk carbides to the X-ray absorption spectra. During the reaction, palladium carbide is formed, which does not lead to a loss of activity. Unusual contraction of the unit cell parameter of the palladium lattice in the spent catalyst was observed upon increasing hydrogen partial pressure.

Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations., Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic., Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing)., Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003)., Conclusion: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5 T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose., Material and Methods: For twenty PC patients treated by 35 Gy (D p ) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (D rec ). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D 95%  ≥ 95%D p to PTV, and D 1cc  ≤ D p to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from D rec . A cumulative dose (D sum ) was calculated from the five daily D rec deformed onto the simulation MRi., Results: For each patient, CTV coverage resulted in D 95%  > 95%D p when estimated as ifa by D rec . No significant difference for D 95% and D 99% metrics to CTV resulted between groups I and II. D 1cc was < D p for rectum, urethral-PRV, and penile bulb, whereas < 103.5%D p for the bladder. Significant correlations resulted between metrics computed by D sum and as ifa by D rec , by both linear-correlation analysis, and Receiver-Operating-Characteristic curve analysis., Conclusions: Our results for PC-SBRT confirm the adequacy of the delivered dose by ATS with 1.5 T MR-linac, and the consistency between dose-volume metrics computed by D rec and D sum ., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Introduction: Covid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic., Method: This observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test., Results: A significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with highly suspected Covid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to "Italian general population" (p = .030, p = .001, p = .000, respectively); and for definite + highly suspected diagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population). Moreover, significantly higher prevalence of definite + highly suspected diagnosis of Covid-19 disease was found either in patients with various "connective tissue diseases" compared to "inflammatory arthritis group" (p < .000), or in patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs treatments (p = .011)., Conclusions: The finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases. Key Points • Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients' increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement. • The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing. • Patients with "connective tissue diseases" show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to "inflammatory arthritis group". • Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.

Aims and Objectives: To conduct a systematic review and meta-synthesis of findings from qualitative research about sexuality and intimate relationship among patients with dermatological diseases., Background: Over the last few decades, there has been an increase in clinical research investigating aspects related to sex and sexuality in patients living with dermatological diseases. In fact, studies recognise a negative impact on various aspects of intimacy, such as sexual function, self-esteem and romantic relationships. The body of qualitative literature about sexuality in the context of dermatological diseases is emerging but consists mainly of small studies that would benefit from aggregation, synthesis and interpretation to highlight and summarise the overarching dimensions to this clinical issue., Design: A systematic review and meta-synthesis of qualitative studies., Methods: BioMed Central, Cochrane Library, MEDLINE, CINAHL, PsycINFO, PsycARTICLES, ERIC, Scopus, and Web of Science were searched between June-November 2017 with no publication date limits. Screening and selection of studies was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). After retrieval, the qualitative data were subject to meta-synthesis to identify overarching themes., Results: Ten qualitative studies were found. We identified four themes: (a) Embarrassment and shame; (b) Impaired sense of attractiveness and sexual avoidance; (c) Relationship issues; and (d) Lack of professional support. The patients in these studies adopted negative coping styles, such as avoidance and hiding their bodies., Conclusion: When assessing and evaluating patient care in dermatology, it is important that sexuality and the impact the disease could have on relationships is included., Relevance to Clinical Practice: An important part of nursing care is ensuring that patients are helped to develop positive coping strategies rather than negative ones. Patients with dermatological conditions also need advice and treatment to address any physically related sexual problems. Nurses need to be the initiators of these sensitive conversations to put patients at ease and work together to implement positive measures to reduce the sexuality-related issues patients face., (© 2020 John Wiley & Sons Ltd.)

Purpose: A CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy is the standard of care for patients with hormone receptor-positive (HR+) and HER2-negative (HER2-) metastatic breast cancer (MBC). However, the incorporation of these agents into clinical practice remains challenging. This study aims to estimate the impact of the lack of access to ribociclib on mortality of premenopausal patients with MBC in Brazil., Methods: Based on published epidemiological studies and national cancer registries, we estimated the number of premenopausal patients with potential indication of ribociclib as first-line treatment for MBC. Efficacy estimates were based on results from the Monaleesa-7 trial. Our analysis is made under the unrealistic assumption that all premenopausal MBC patients would be candidates for the treatment. To estimate the number of yearly premature deaths that could be prevented, we considered the largest absolute effect on mortality when sequentially applying the observed hazard ratio., Results: We estimated an annual incidence of 4,294 premenopausal HR+, HER2- MBC patients in Brazil. Considering these patients, at 12, 24 and 60 months, the number of surviving subjects would be 3,504, 2,859 and 1,553 for endocrine therapy (ET) alone; and 3,717, 3,217 and 2,086 for ET plus ribociclib. The largest difference between both groups was observed at the end of the sixth year when the use of ribociclib would prevent 538 premature deaths (survival of 1,805 versus 1,267 patients by the 72nd month)., Conclusion: We estimate that lack of access to CDK4/6i for patients with HR+, HER2-, MBC will cause the premature death of a significant number of premenopausal women with MBC. The unavailability of effective therapies has measurable consequences. Progress in this area demands a concerted effort to prevent further loss of lives., Competing Interests: Tomás Reinert: Speaker honoraria: Novartis, AstraZeneca, Pfizer, Libbs, Lilly, Pierre FabreConsulting or advisory role: AstraZeneca, Lilly, NovartisResearch funding: AstraZenecaRodrigo Pellegrino: noneCarlos Henrique Barrios: Stock and other ownership interests: Biomarker, MedSIR, TummiSpeaker honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, EisaiConsulting or advisory role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Libbs, MSD Oncology, United MedicalResearch funding: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, Biomarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis BioScience, AB Science, Asana Biosciences, Medivation, Exelixis, ImClone Systems, LEO Pharma, Millennium, Janssen, Atlantis Clinica, INC Research, Halozyme, Covance, Celgene, inVentiv HealthTravel, accommodations, expenses: Roche/Genentech, Novartis, Pfizer, BMS Brazil, AstraZeneca, MSD Oncology, (© the authors; licensee ecancermedicalscience.)

Purpose: To develop and validate a robust template for VMAT SBRT of lung lesions, using the multicriterial optimization (MCO) of a commercial treatment planning system., Methods: The template was established and refined on 10 lung SBRT patients planned for 55 Gy/5 fr. To improve gradient and conformity a ring structure around the planning target volume (PTV) was set in the list of objectives. Ideal fluence optimization was conducted giving priority to organs at risk (OARs) and using the MCO, which further pushes OARs doses. Segmentation was conducted giving priority to PTV coverage. Two different templates were produced with different degrees of modulation, by setting the Fluence Smoothing parameter to Medium (MFS) and High (HFS). Each template was applied on 20 further patients. Automatic and manual plans were compared in terms of dosimetric parameters, delivery time, and complexity. Statistical significance of differences was evaluated using paired two-sided Wilcoxon signed-rank test., Results: No statistically significant differences in PTV coverage and maximum dose were observed, while an improvement was observed in gradient and conformity. A general improvement in dose to OARs was seen, which resulted to be significant for chest wall V 30 Gy , total lung V 20 Gy , and spinal cord D 0.1 cc . MFS plans are characterized by a higher modulation and longer delivery time than manual plans. HFS plans have a modulation and a delivery time comparable to manual plans, but still present an advantage in terms of gradient., Conclusion: The automation of the planning process for lung SBRT using robust templates and MCO was demonstrated to be feasible and more efficient., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)