Personalized surveillance and aftercare for non-metastasized breast cancer:the NABOR study protocol of a multiple interrupted time series design

Background: Follow-up of curatively treated primary breast cancer patients consists of surveillance and aftercare and is currently mostly the same for all patients. A more personalized approach, based on patients’ individual risk of recurrence and personal needs and preferences, may reduce patient burden and reduce (healthcare) costs. The NABOR study will examine the (cost-)effectiveness of personalized surveillance (PSP) and personalized aftercare plans (PAP) on patient-reported cancer worry, self-rated and overall quality of life and (cost-)effectiveness.Methods: A prospective multicenter multiple interrupted time series (MITs) design is being used. In this design, 10 participating hospitals will be observed for a period of eighteen months, while they -stepwise- will transit from care as usual to PSPs and PAPs. The PSP contains decisions on the surveillance trajectory based on individual risks and needs, assessed with the ‘Breast Cancer Surveillance Decision Aid’ including the INFLUENCE prediction tool. The PAP contains decisions on the aftercare trajectory based on individual needs and preferences and available care resources, which decision-making is supported by a patient decision aid. Patients are non-metastasized female primary breast cancer patients (N = 1040) who are curatively treated and start follow-up care. Patient reported outcomes will be measured at five points in time during two years of follow-up care (starting about one year after treatment and every six months thereafter). In addition, data on diagnostics and hospital visits from patients’ Electronical Health Records (EHR) will be gathered. Primary outcomes are patient-reported cancer worry (Cancer Worry Scale) and overall quality of life (as assessed with EQ-VAS score). Secondary outcomes include health care costs and resource use, health-related quality of life (as measured with EQ5D-5L/SF-12/EORTC-QLQ-C30), risk perception, shared decision-making, patient satisfaction, societal participation, and cost-effectiveness. Next, the uptake and appreciation of personalized plans and patients’ experiences of their decision-making process will be evaluated. Discussion: This study will contribute to insight in the (cost-)effectiveness of personalized follow-up care and contributes to development of uniform evidence-based guidelines, stimulating sustainable implementation of personalized surveillance and aftercare plans. Trial registration: Study sponsor: ZonMw. Retrospectively registered at ClinicalTrials.gov (2023), ID: NCT05975437.</p

Genotoxicity and mutagenicity of Echinodorus macrophyllus (chapéu-de-couro) extracts

Echinodorus macrophyllus, commonly known as chapéu-de-couro, is a medicinal plant used in folk medicine to treat inflammation and rheumatic diseases. In this work, we used short-term bacterial assays based on the induction of SOS functions to examine the genotoxicity and mutagenicity of an aqueous extract of E. macrophyllus leaves. Whole extract and an ethyl acetate fraction showed similar genotoxicity and caused an ~70-fold increase in lysogenic induction. The extract also gave a positive result in the SOS chromotest with an increase of 12-fold in β-Galactosidase enzymatic units. There was a strong trend towards base substitutions and frameshifts at purine sites in the mutations induced by the extract in Escherichia coli (CC103 and CC104 strains) and Salmonella typhimurium test strains (22-fold increase in histidine revertants in TA98 strain). Since reactive oxygen species may be implicated in aging process and in degenerative diseases, we used antioxidant compounds as catalase, thiourea and dipyridyl in the lysogenic induction test. All this compounds were able to reduce the induction factor observed in the treatment with chapéu-de-couro, thus suggesting that the genotoxicity and mutagenicity were attributable to the production of reactive oxygen species that targeted DNA purines

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II)

Background: At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. Methods: In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3–4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. Discussion: The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. Trial registration: clinicaltrials.gov NCT03348150; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing

Serum metabolome associated with severity of acute traumatic brain injury

Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain

Occurrence and timing of withdrawal of life-sustaining measures in traumatic brain injury patients: a CENTER-TBI study

Funder: National Institute for Health Research (UK)Abstract: Background: In patients with severe brain injury, withdrawal of life-sustaining measures (WLSM) is common in intensive care units (ICU). WLSM constitutes a dilemma: instituting WLSM too early could result in death despite the possibility of an acceptable functional outcome, whereas delaying WLSM could unnecessarily burden patients, families, clinicians, and hospital resources. We aimed to describe the occurrence and timing of WLSM, and factors associated with timing of WLSM in European ICUs in patients with traumatic brain injury (TBI). Methods: The CENTER-TBI Study is a prospective multi-center cohort study. For the current study, patients with traumatic brain injury (TBI) admitted to the ICU and aged 16 or older were included. Occurrence and timing of WLSM were documented. For the analyses, we dichotomized timing of WLSM in early (< 72 h after injury) versus later (≥ 72 h after injury) based on recent guideline recommendations. We assessed factors associated with initiating WLSM early versus later, including geographic region, center, patient, injury, and treatment characteristics with univariable and multivariable (mixed effects) logistic regression. Results: A total of 2022 patients aged 16 or older were admitted to the ICU. ICU mortality was 13% (n = 267). Of these, 229 (86%) patients died after WLSM, and were included in the analyses. The occurrence of WLSM varied between regions ranging from 0% in Eastern Europe to 96% in Northern Europe. In 51% of the patients, WLSM was early. Patients in the early WLSM group had a lower maximum therapy intensity level (TIL) score than patients in the later WLSM group (median of 5 versus 10) The strongest independent variables associated with early WLSM were one unreactive pupil (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.3–12.4) or two unreactive pupils (OR 5.8, CI 2.6–13.1) compared to two reactive pupils, and an Injury Severity Score (ISS) if over 41 (OR per point above 41 = 1.1, CI 1.0–1.1). Timing of WLSM was not significantly associated with region or center. Conclusion: WLSM occurs early in half of the patients, mostly in patients with severe TBI affecting brainstem reflexes who were severely injured. We found no regional or center influences in timing of WLSM. Whether WLSM is always appropriate or may contribute to a self-fulfilling prophecy requires further research and argues for reluctance to institute WLSM early in case of any doubt on prognosis

Three-dimensional deuterium-carbon correlation experiments for high-resolution solid-state mas nmr spectroscopy of large proteins

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