Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; Potential marker of disease recurrence

Background: Epigenetic alterations of specific genes have been reported to be related to colorectal cancer (CRC) transformation and would also appear to be involved in the early stages of colorectal carcinogenesis. Little data are available on the role of these alterations in determining a different risk of colorectal lesion recurrence. The aim of the present study was to verify whether epigenetic alterations present in pre-neoplastic colorectal lesions detected by colonoscopy can predict disease recurrence. Methods. A retrospective series of 78 adenomas were collected and classified as low (35) or high-risk (43) for recurrence according to National Comprehensive Cancer Network guidelines. Methylation alterations were analyzed by the methylation-specific multiplex ligation probe assay (MS-MLPA) which is capable of quantifying methylation levels simultaneously in 24 different gene promoters. MS-MLPA results were confirmed by pyrosequencing and immunohistochemistry. Results: Higher levels of methylation were associated with disease recurrence. In particular, MLH1, ATM and FHIT gene promoters were found to be significantly hypermethylated in recurring adenomas. Unconditional logistic regression analysis used to evaluate the relative risk (RR) of recurrence showed that FHIT and MLH1 were independent variables with an RR of 35.30 (95% CI 4.15-300.06, P = 0.001) and 17.68 (95% CI 1.91-163.54, P = 0.011), respectively. Conclusions: Histopathological classification does not permit an accurate evaluation of the risk of recurrence of colorectal lesions. Conversely, results from our methylation analysis suggest that a classification based on molecular parameters could help to define the mechanisms involved in carcinogenesis and prove an effective method for identifying patients at high risk of recurrence

Protein Array Profiling of Tic Patient Sera Reveals a Broad Range and Enhanced Immune Response against Group A Streptococcus Antigens

The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS) is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS antigen-dependent induction of autoantibodies in susceptible individuals may be involved the occurrence of tic disorders

Quality of Life in Older Adults After Major Cancer Surgery:The GOSAFE International Study

Abstract Background Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL. Methods GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale. Results Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P < .001). Domains showing improvement were pain and anxiety or depression. A Flemish Triage Risk Screening Tool score greater than or equal to 2 (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.13 to 2.21, P = .007), palliative surgery (OR = 2.14, 95% CI = 1.01 to 4.52, P = .046), postoperative complications (OR = 1.95, 95% CI = 1.19 to 3.18, P = .007) correlated with worsening QoL. Conclusions GOSAFE shows that older adults’ preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients’ expectations

Psychosocial treatment on psychological symptoms, adherence, and physiological function on transplanted patients: A systematic review and metanalysis

Objective: Transplantation represents an important source of hope for the candidates and produces an intense emotional effect. Psychosocial interventions can be helpful in all transplantation stages to better manage this extraordinarily stressful situation. Aim of the work is to verify the effects of the psychosocial interventions on recipients on psychological symptoms, medical adherence and transplanted solid organ functioning. Methods: This work adhered to PRISMA, STROBE, Cochrane and New Castle Ottawa bias scales and it is registered in PROSPERO. Inserting “Transplant” and “Psychological intervention” as key words in PubMed, Psycinfo, Cochrane database resulted 977 studies from 2001 to 2021. A systematic review and metanalyses were processed on nineteen randomized controlled trials and observative prospective cohort studies. The difference between preand post- psychosocial intervention assessment on the psychological variables, medical adherence, and organ functioning outcome was processed. Results: Main findings showed that the psychosocial interventions were effective on depression (0.62; CI: 0.32–0.92) and anxiety on kidney recipients (0.49; CI: 0.17–0.81), and on anxiety on heart recipients, mainly when administrated after the surgery (0.68; CI: 0.30–1.06). Moreover, the findings showed a lack of studies on the effectiveness of the psychosocial intervention on organ functioning. Conclusion: The work highlighted the effectiveness of the psychosocial interventions on psychological outcome, particularly after the surgery and the need to address the research on the evaluation of the effectiveness of the psychosocial interventions on the organ functioning. The findings suggest to integrate the transplantation procedures with psychosocial interventions considering the different needs of recipients in relation to the specific transplanted organ

A Single Institution's 27-Year Surgical Experience with Pancreatic Neuroendocrine Tumors: Time Trends, Comparison of Current Staging Systems and Outcome Analysis

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Digital Guardian Angel Supported by an Artificial Intelligence System to Improve Quality of Life, Well-being, and Health Outcomes of Patients With Cancer (ONCORELIEF): Protocol for a Single Arm Prospective Multicenter Pilot Study

BackgroundAccording to Europe’s Beating Cancer Plan, the number of cancer survivors is growing every year and is now estimated at over 12 million in Europe. A main objective of the European Commission is to ensure that cancer survivors can enjoy a high quality of life, underlining the role of digital technology and eHealth apps and tools to achieve this. ObjectiveThe main objective of this study is the development of a user-centered artificial intelligence system to facilitate the input and integration of patient-related biopsychosocial data to improve posttreatment quality of life, well-being, and health outcomes and examine the feasibility of this digitally assisted workflow in a real-life setting in patients with colorectal cancer and acute myeloid leukemia. MethodsA total of 60 patients with colorectal cancer and 30 patients with acute myeloid leukemia will be recruited from 2 clinical centers: Universitätsmedizin der Johannes Gutenberg-Universität Mainz (Mainz, Germany) and IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” (IRST, Italy). Psychosocial data (eg, emotional distress, fatigue, quality of life, subjective well-being, sleep problems, and appetite loss) will be collected by questionnaires via a smartphone app, and physiological data (eg, heart rate, skin temperature, and movement through step count) will be collected by a customizable smart wrist-worn sensor device. Each patient will be assessed every 2 weeks over their 3-month participation in the ONCORELIEF study. Inclusion criteria include patients with the diagnosis of acute myeloid leukemia or colorectal cancer, adult patients aged 18 years and older, life expectancy greater than 12 months, Eastern Cooperative Oncology Group performance status ≤2, and patients who have a smartphone and agree to use it for the purpose of the study. Exclusion criteria include patients with a reduced cognitive function (such as dementia) or technological illiteracy and other known active malignant neoplastic diseases (patients with a medical history of treated neoplastic disease are included). ResultsThe pilot study started on September 1, 2022. As of January 2023, we enrolled 33 patients with colorectal cancer and 7 patients with acute myeloid leukemia. As of January 2023, we have not yet started the data analysis. We expect to get all data in June 2023 and expect the results to be published in the second semester of 2023. ConclusionsWeb-based and mobile apps use methods from mathematical decision support and artificial intelligence through a closed-loop workflow that connects health professionals and patients. The ONCORELIEF system has the potential of continuously identifying, collecting, and processing data from diverse patient dimensions to offer health care recommendations, support patients with cancer to address their unmet needs, and optimize survivorship care. Trial RegistrationGerman Clinical Trials Register (DRKS) 00027808; https://drks.de/search/en/trial/DRKS00027808 International Registered Report Identifier (IRRID)DERR1-10.2196/4547

Personalizing precision medicine : Patients with AML perceptions about treatment decisions

Background: This study aims to explore patients' with acute myeloid leukemia perceptions about precision medicine and their preferences for involvement in this new area of shared decision-making.Methods: Individual semi-structured interviews were conducted in Finland, Italy and Germany (n = 16). The study population included patients aged 24-79 years. Interviews were analyzed with thematic content analysis.Results: Patient's perceived lack of knowledge as a barrier for their involvement in decision-making. Treatment decisions were often made rapidly based on the patient's intuition and trust for the physician rather than on information, in situations that decrease the patient's decision capacity. The patients emphasized that they are in a desperate situation that makes them willing to accept treatment with low probabilities of being cured.Conclusions: The study raised important issues regarding patients' understanding of precision medicine and challenges concerning how to involve patients in medical decision-making. Although technical advances were viewed positively, the role of the physician as an expert and person-of-trust cannot be replaced. Practice implications: Regardless of patients' preferences for involvement in decision-making, information plays a crucial role for patients' perceived involvement in their care. The concepts related to precision medicine are complex and will imply challenges to patient education.Peer reviewe