Gender oncology: recommendations and consensus of the Italian Association of Medical Oncology (AIOM).

BACKGROUND: Following the development of gender medicine in the past 20 years, more recently in the field of oncology an increasing amount of evidence suggests gender differences in the epidemiology of cancers, as well as in the response and toxicity associated with therapies. In a gender approach, critical issues related to sexual and gender minority (SGM) populations must also be considered. MATERIALS AND METHODS: A working group of opinion leaders approved by the Italian Association of Medical Oncology (AIOM) has been set up with the aim of drafting a shared document on gender oncology. Through the 'consensus conference' method of the RAND/University of California Los Angeles (UCLA) variant, the members of the group evaluated statements partly from the scientific literature and partly produced by the experts themselves [good practice points (GPPs)], on the following topics: (i) Healthcare organisation, (ii) Therapy, (iii) Host factors, (iv) Cancer biology, and (v) Communication and social interventions. Finally, in support of each specific topic, they considered it appropriate to present some successful case studies. RESULTS: A total of 42 articles met the inclusion criteria, from which 50 recommendations were extracted. Panel participants were given the opportunity to propose additional evidence from studies not included in the research results, from which 32 statements were extracted, and to make recommendations not derived from literature such as GPPs, four of which have been developed. After an evaluation of relevance by the panel, it was found that 81 recommendations scored >7, while 3 scored between 4 and 6.9, and 2 scored below 4. CONCLUSIONS: This consensus and the document compiled thereafter represent an attempt to evaluate the available scientific evidence on the theme of gender oncology and to suggest standard criteria both for scientific research and for the care of patients in clinical practice that should take gender into account.

Prognostic impact of pretreatment cell-free DNA concentration in newly diagnosed peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.

Etiology, presentation and management of urinary tract infections in multiple sclerosis patients: A review of the current literature.

Urinary tract infections (UTIs) present a formidable challenge in the care of individuals affected by multiple sclerosis (MS). Lower urinary tract dysfunction is a prevalent issue among MS patients, predisposing them to an elevated risk of UTIs. When left untreated, UTIs can further exacerbate the already compromised quality of life in individuals with MS. The diagnosis and management of UTIs in MS patients necessitate a careful clinical evaluation. The objective of this review is to delineate preventive strategies and current and developing therapeutic approaches for preventing and treating UTIs associated with urinary dysfunction, catheterization, and upper urinary tract infections in patients with MS. Effectively addressing UTIs and urinary tract dysfunction in individuals with multiple sclerosis calls for a comprehensive, interdisciplinary approach.

Robustness analysis of surface-guided DIBH left breast radiotherapy: personalized dosimetric effect of real intrafractional motion within the beam gating thresholds.

PURPOSE: The robustness of surface-guided (SG) deep-inspiration breath-hold (DIBH) radiotherapy (RT) for left breast cancer was evaluated by investigating any potential dosimetric effects due to the residual intrafractional motion allowed by the selected beam gating thresholds. The potential reduction of DIBH benefits in terms of organs at risk (OARs) sparing and target coverage was evaluated for conformational (3DCRT) and intensity-modulated radiation therapy (IMRT) techniques. METHODS: A total of 192 fractions of SGRT DIBH left breast 3DCRT treatment for 12 patients were analyzed. For each fraction, the average of the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift") during beam-on was evaluated and applied to the original plan isocenter. The dose distribution for the treatment beams with the new isocenter point was then calculated and the total plan dose distribution was obtained by summing the estimated perturbed dose for each fraction. Then, for each patient, the original plan and the perturbed one were compared by means of Wilcoxon test for target coverage and OAR dose-volume histogram (DVH) metrics. A global plan quality score was calculated to assess the overall plan robustness against intrafractional motion of both 3DCRT and IMRT techniques. RESULTS: Target coverage and OAR DVH metrics did not show significant variations between the original and the perturbed plan for the IMRT techniques. 3DCRT plans showed significant variations for the left descending coronary artery (LAD) and the humerus only. However, none of the dose metrics exceeded the mandatory dose constraints for any of the analyzed plans. The global plan quality analysis indicated that both 3DCRT and IMRT techniques were affected by the isocenter shifts in the same way and, generally, the residual isocenter shifts more likely tend to worsen the plan in all cases. CONCLUSION: The DIBH technique proved to be robust against residual intrafractional isocenter shifts allowed by the selected SGRT beam-hold thresholds. Small-volume OARs located near high dose gradients showed significant marginal deteriorations in the perturbed plans with the 3DCRT technique only. Global plan quality was mainly influenced by patient anatomy and treatment beam geometry rather than the technique adopted.

EURADOS ISO/IEC 17025 guidance for IMS: suggestions on how to interpret and implement the requirements including examples from accredited laboratories.

Individual monitoring of external radiation is an activity usually regulated by national regulatory bodies in most countries. Regulations generally contain technical requirements to be met by the individual monitoring services (IMS), in order to ensure that the measurements are correct and therefore the dosimetry results are reliable. In some countries, the requirements include or even consist of the accreditation of the service according to the standard ISO/IEC 17025: 'General requirements for the competence of testing and calibration laboratories.' It is a fact that accreditation is a growing trend among European IMS as a way to guarantee confidence in their technical competence. The acceptance of the dosimetry results between countries and their indentation in the respective National Dose Registries is facilitated if laboratories conform to the ISO/IEC 17025 standard. In the framework of the activities of EURADOS (European Radiation Dosimetry Group) working group 2 'Harmonization of Individual Monitoring in Europe' and attending to the concern of many European IMS in the process of accreditation, a guide has been prepared. The purpose was to assist and encourage IMS to apply for accreditation and to share the authors' own experience with the process. The guide intends to be a practical reference for IMS on how to interpret and implement the ISO/IEC 17025 requirements to the specific activity of a personal dosimetry service for external radiation, emphasizing those aspects of special interest. It includes examples from dosimetry laboratories already accredited. The major novelties from a new edition of ISO/IEC 17025: 2017 are also identified in the guide. Finally, the guide aims to assist the auditing process, giving examples of auditor's questions and how to show evidence of compliance. The main findings are presented.

Built-in tensile strain dependence on the lateral size of monolayer MoS2 synthesized by liquid precursor chemical vapor deposition.

Strain engineering is an efficient tool to tune and tailor the electrical and optical properties of 2D materials. The built-in strain can be tuned during the synthesis process of a two-dimensional semiconductor, such as molybdenum disulfide, by employing different growth substrates with peculiar thermal properties. In this work, we demonstrate that the built-in strain of MoS2 monolayers, grown on a SiO2/Si substrate by liquid precursor chemical vapor deposition, is mainly dependent on the size of the monolayer. In fact, we identify a critical size equal to 20 µm, from which the built-in strain increases drastically. The built-in strain is the maximum for a 60 µm sized monolayer, leading to 1.2% tensile strain with a partial release of strain close to the monolayer triangular vertexes due to the formation of nanocracks. These findings also imply that the standard method for evaluation of the number of layers based on the Raman mode separation can become unreliable for highly strained monolayers with a lateral size above 20 µm.

A retrospective study on bone metastasis in dogs with advanced-stage solid cancer.

OBJECTIVES: To review clinical characteristics, treatment, outcome and prognostic factors in dogs with solid cancer-bearing bone metastases. MATERIALS AND METHODS: Records were reviewed from dogs with histologically-proven solid cancer and bone metastases. Clinicopathologic variables, bone metastases characteristics and skeletal-related events were recorded. Endpoints were time to bone metastases and survival. RESULTS: Fifty dogs were included, 20 of them with synchronous and 30 of them with metachronous bone metastases. In the latter group, median time to diagnosis of bone metastases was 210 days (range, 30 to 1835). Most common primary cancer locations included mammary gland (n=6), spleen (n=5) and tonsil (n=5). Most common histotypes were carcinoma (n=32) and hemangiosarcoma (n=10). Nineteen dogs had multiple bones involvement, with humeri and vertebrae more commonly affected. Twenty-four dogs received antitumoural therapy, five symptomatic treatment and 21 were not treated. Overall median survival after bone metastases diagnosis was 30 days (range, 11 to 49); 83% of dogs died because of skeletal-related events. Lack of antitumoural therapy was significantly associated with shorter survival (hazard ratio: 2.7; 95% confidence interval: 1.3 to 5.6) and with increased risk of skeletal-related death (hazard ratio: 3.3; 95% confidence interval: 1.4 to 7.4). Dogs with endocrine/neuroendocrine tumours (odds ratio: 8.8; 95% confidence interval: 1.2 to 63.9), without appendicular metastases (odds ratio: 5.1; 95% confidence interval: 1.0 to 25.8), without extra-skeletal metastases (odds ratio: 5.2; 95% confidence interval: 1.1 to 24.5) and receiving antitumoural therapy (odds ratio: 14.8; 95% confidence interval: 1.7 to 131.4) had an increased chance of surviving more than 100 days. CLINICAL SIGNIFICANCE: Bone metastases in dogs with solid cancers are associated with poor prognosis and a high risk of skeletal-related events. Treatment appears to have an impact on survival.

Surface-guided DIBH radiotherapy for left breast cancer: impact of different thresholds on intrafractional motion monitoring and DIBH stability.

PURPOSE: To compare two left breast cancer patient cohorts (tangential vs. locoregional deep-inspiration breath-hold - DIBH treatment) with different predefined beam gating thresholds and to evaluate their impact on motion management and DIBH stability. METHODS: An SGRT-based clinical workflow was adopted for the DIBH treatment. Intrafractional monitoring was performed by tracking both the respiratory signal and the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift"). Beam gating tolerances were 5 mm/4 mm for the SGRT shifts and 5 mm/3 mm for the gating window amplitude for breast tangential and breast + lymph nodes locoregional treatments, respectively. A total of 24 patients, 12 treated with a tangential technique and 12 with a locoregional technique, were evaluated for a total number of 684 fractions. Statistical distributions of SGRT shift and respiratory signal for each treatment fraction, for each patient treatment, and for the two population samples were generated. RESULTS: Lateral cumulative distributions of SGRT shifts for both locoregional and tangential samples were consistent with a null shift, whereas longitudinal and vertical ones were slightly negative (mean values < 1 mm). The distribution of the percentage of beam on time with SGRT shift > 3 mm, > 4 mm, or > 5 mm was extended toward higher values for the tangential sample than for the locoregional sample. The variability in the DIBH respiration signal was significantly greater for the tangential sample. CONCLUSION: Different beam gating thresholds for surface-guided DIBH treatment of left breast cancer can impact motion management and DIBH stability by reducing the frequency of the maximum SGRT shift and increasing respiration signal stability when tighter thresholds are adopted.

CT features of gastrointestinal spindle cell, epithelial, and round cell tumors in 41 dogs.

There is sparse published information on computed tomographic (CT) characteristics of canine gastrointestinal tumors. The purposes of this multi-center, retrospective, descriptive study were to describe the CT features of histologically-confirmed canine gastrointestinal spindle cell, epithelial, and round cell tumors and, when available, describe the corresponding ultrasound findings. The inclusion criteria were as follows: availability of pre-and post-contrast CT study, and a histopathological diagnosis of the lesions. Recorded parameters were tumor size, location, gastrointestinal wall layers involvement, lesion's growth and enhancement patterns, tumor margination, presence of stenosis, mineralization, ulcerations, lymphadenopathy, or other lesions in the abdomen/thorax. When available, ultrasound images were evaluated. Forty-one dogs met the inclusion criteria and had the following histological diagnoses: 21/41 (51%) spindle cells (7 leiomyomas, 14 leiomyosarcomas/gastrointestinal stromal tumors (GISTs)), 13/41 (32%) epithelial (adenocarcinoma), and 7/41 (17%) round cell (lymphoma) tumors. The growth pattern was concentric, eccentric, and mixed in epithelial, spindle cell, and round cell tumors, respectively. Spindle cell tumors had the largest main volume and involved the outer gastrointestinal layer with an unaffected inner layer. Leiomyosarcomas/GISTs showed irregular margins compared to leiomyomas. Only lymphomas showed multifocal gastrointestinal involvement. Nine carcinomas and six spindle cell tumors caused partial stenosis with secondary sub-obstruction. Mineralizations were more frequent in spindle cell tumors (10/21) and absent in lymphomas. Lymphadenomegaly was widespread in lymphomas, regional in leiomyosarcomas-GISTs and adenocarcinomas, and absent in leiomyomas. The reported CT features may be useful in prioritizing the differential diagnosis between spindle cell, epithelial, and round cell tumors, similar to those reported on ultrasound.

Atrial fibrillation: Epigenetic aspects and role of sodium-glucose cotransporter 2 inhibitors.

Atrial fibrillation (AF) is the most frequent arrhythmia and is associated with substantial morbidity and mortality. Pathophysiological aspects consist in the activation of pro-fibrotic signaling and Ca2+ handling abnormalities at atrial level. Structural and electrical remodeling creates a substrate for AF by triggering conduction abnormalities and cardiac arrhythmias. The care of AF patients focuses predominantly on anticoagulation, symptoms control and the management of risk factors and comorbidities. The goal of AF therapy points to restore sinus rhythm, re-establish atrioventricular synchrony and improve atrial contribution to the stroke volume. New layer of information to better comprehend AF pathophysiology, and identify targets for novel pharmacological interventions consists of the epigenetic phenomena including, among others, DNA methylation, histone modifications and noncoding RNAs. Moreover, the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in diabetic and non-diabetic patients at cardiovascular risk as well as emerging evidence on the ability of SGLT2i to modify epigenetic signature in cardiovascular diseases provide a solid background to investigate a possible role of this drug class in the onset and progression of AF. In this review, following a summary of pathophysiology and management, epigenetic mechanisms in AF and the potential of sodium-glucose SGLT2i in AF patients are discussed.

Interaction of methyl-jasmonate and Fusarium poae in bread wheat.

Fusarium Head Blight (FHB) is a devastating disease that affects the grain yield and quality of essential crops such as wheat. In the last years, some Fusarium species have acquired particular importance as Fusarium poae. However, studies to evaluate F. poae-wheat interaction are still scarce. The interaction between F. poae and two bread wheat cultivars with different resistance levels against FHB was evaluated. Moreover, the application of methyl-jasmonate (MeJA) was evaluated as a possible tool to reduce the fungal presence. Our results showed that the MeJA treatment is isolate-dependent, reducing F. poae fungal growth. A decrease in fungal biomass was observed in the susceptible cultivar after MeJA application; however, no differences between inoculated and inoculated-MeJA treatments were observed in the resistant cultivar. Finally, the F. poae inoculation induces the expression of PR1-1 and PDF 1.2, being early in the resistant cultivar compared to the susceptible ones. The application of MeJA combined with the F. poae inoculation increased PR1-1 and PDF1.2 expressions in resistant cultivars. To our knowledge, this is the first study that evaluates the interaction between F. poae and wheat and the MeJA treatment as a possible management strategy against this important pathogen.

Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures.

PURPOSE: This study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures. METHODS: The procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored. All procedures were performed with table-mounted and ceiling-suspended shields (0.5 mm lead equivalent thickness), except for FEVAR and PM-ICD where only a table mounted shield was present, and CT-guided lung biopsy where no shield was used. Dose assessment was performed using a dosemeter positioned close to the most exposed eye of the surgeon, outside the protective eyewear. RESULTS: The surgeon most exposed eye lens median Hp(3) equivalent dose for a single procedure, without protective eyewear contribution, was 18 µSv for neuroradiology diagnostic study, 62 µSv for AVM, 38 µSv for aneurysm embolization, 33 µSv for CA-PTCA, 39 µSv for PM-ICD, 49 µSv for EVAR, 2500 µSv for FEVAR, 153 µSv for CT-guided lung biopsy. CONCLUSIONS: In interventional procedures, the 20 mSv/year dose limit for surgeon eye lens exposure might be exceeded if shields or protective eyewear are not used. Surgeon eye lens doses, normalised to single procedures and to exposure parameters, are a valuable tool for determining appropriate radiation protection measures and dedicated eye lens dosemeter assignment.

Stranded pellets in Fildes Peninsula (King George Island, Antarctica): New evidence of Southern Ocean connectivity.

Plastic and microplastic debris is transported by ocean currents over long distances, reaching remote areas, far from its original source. In Polar Regions, microplastics (MPs) can come from local activities or be transported from lower latitudes, with the former being the likely and major source. Although historically Antarctica was considered isolated from the global ocean, there is recent evidence of materials and organisms being transported in and out of the Southern Ocean, despite its multi-front structure. During the austral summer of 2019, beach surveys were conducted on the NW coast of the Fildes Peninsula (King George Island). The beach was characterised, and the first 2 cm of sediment from 5 quadrants (50 × 50 cm) along 100 m of the highest strandline were collected. Large microplastics (LMPs) and mesoplastics (MesoPs) were isolated, counted, measured, weighed and classified by shape. Polymer composition was analysed by FTIR and ageing estimated by Carbonyl Index. We found 293 items of LMPs (188 items) and MesoPs (105 items), with a total average density (±SD) of 234.4 ± 166 items m-2. Foams (130.4 ± 76.3), fragments (58.4 ± 56.0) and pellets (44.0 ± 50.5) were the most abundant shapes. The main polymers found were polystyrene, polypropylene, and polyethylene. We found pellets among the MesoPs, being the first record for beaches in Antarctica. The presence of these primary MPs south of 62°S not only alerts about their possible direct consequences on Antarctic ecosystems, but also gives empirical evidence for the passive entry of plastic debris from lower latitudes through cross-frontal exchanges, providing new evidence of a global connectivity of the Southern Ocean. Despite increasing research, knowledge of plastics dynamics and their impact in the Southern Ocean and Antarctica is still limited but certainly necessary.

Acute toxic exposures in children: analysis of a three year registry managed by a Pediatric poison control Center in Italy.

INTRODUCTION: Acute pediatric poisoning is an emerging health and social problem. The aim of this study is to describe the characteristics of a large pediatric cohort exposed to xenobiotics, through the analysis of a Pediatric Poison Control Center (PPCc) registry. METHODS: This study, conducted in the Pediatric Hospital Bambino Gesù of Rome, a reference National Pediatric Hospital, collected data of children whose parents or caregivers contacted the PPCc by phone (group "P"), or who presented to the Emergency Department (group "ED"), during the three-year period 2014-2016. Data were prospectively and systematically collected in a pre-set electronic registry. Comparisons among age groups were performed and multivariable logistic regression models used to investigate associations with outcomes (hospital referral for "P", and hospital admission for "ED"group). RESULTS: We collected data of 1611 children on group P and 1075 on group ED. Both groups were exposed to both pharmaceutical and non-pharmaceutical agents. Pharmaceutical agent exposure increased with age and the most common route of exposure was oral. Only 10% among P group were symptomatic children, with gastrointestinal symptoms. Among the ED patients, 30% were symptomatic children mostly with gastrointestinal (55.4%) and neurologic symptoms (23.8%). Intentional exposure (abuse substance and suicide attempt), which involved 7.7% of patients, was associated with older age and Hospital admission. CONCLUSIONS: Our study describes the characteristics of xenobiotics exposures in different paediatric age groups, highlighting the impact of both pharmacological and intentional exposure. Furthermore, our study shows the utility of a specific PPCc, either through Phone support or by direct access to ED. PPCc phone counselling could avoid unnecessary access to the ED, a relevant achievement, particularly in the time of a pandemic.

Impact of new operational dosimetric quantities on individual monitoring services.

The new operational dosimetric quantities framework, proposed in the ICRU95 report, has stimulated the scientific community to start investigations that aim to assess its impact on radiation protection practices. As part of this effort, the present study describes an inter-comparison exercise among individual monitoring services (IMSs) on passive whole-body dosimetry. The inter-comparison is performed in terms of both the existing operational dose quantityHp(10)and its proposed replacementHp, to allow an evaluation of the actions that may be necessary to adapt dosimetry systems to the proposed quantity. For two of the tested IMSs, simple modifications to the detector response function, or the dose calculation algorithm, were sufficient to obtain results within acceptable limits. However, these approaches are not sufficient to give a level of performance comparable to that achieved in terms ofHp(10). This may require a modification to dosemeter design.

Critical points and potential pitfalls of outbreak of IMP-1-producing carbapenem-resistant Pseudomonas aeruginosa among kidney transplant recipients: a case-control study.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection after kidney transplantation (KT) is associated with high mortality. AIM: To analyse an outbreak of infection/colonization with IMP-1-producing CRPA on a KT ward. METHODS: A case-control study was conducted. Cases were identified through routine surveillance culture and real-time polymerase chain reaction for carbapenemase performed directly from rectal swab samples. Controls were randomly selected from patients hospitalized on the same ward during the same period, at a ratio of 3:1. Strain clonality was analysed through pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing was performed for additional strain characterization. FINDINGS: CRPA was identified in 37 patients, in 51.4% through surveillance cultures and in 49.6% through clinical cultures. The median persistence of culture positivity was 42.5 days. Thirteen patients (35.1%) presented a total of 15 infections, of which seven (46.7%) were in the urinary tract; among those, 30-day mortality rate was 46.2%. PFGE analysis showed that all of the strains shared the same pulsotype. Multilocus sequence typing analysis identified the sequence type as ST446. Risk factors for CRPA acquisition were hospital stay >10 days, retransplantation, urological surgical reintervention after KT, use of carbapenem or ciprofloxacin in the last three months and low median lymphocyte count in the last three months. CONCLUSION: KT recipients remain colonized by CRPA for long periods and could be a source of nosocomial outbreaks. In addition, a high proportion of such patients develop infection. During an outbreak, urine culture should be added to the screening protocol for KT recipients.