Conectar
by Emily Tufano, Kondaiah Palsa, Rebecka O. Serpa, Timothy B. Helmuth, Gabriela Remit-Berthet, Sara Mills-Huffnagle, Mathias Kant, Aurosman Sahu, James R. Connor
Iron is essential for normal physiological function, yet dysregulation of iron metabolism is increasingly recognized as a hallmark of cancers such as glioblastoma (GBM). Recent clinical evidence suggests that systemic iron deficiency anemia (IDA) negatively impacts GBM outcomes in a sex-dependent manner, but the mechanisms linking systemic iron availability to tumor iron metabolism remain poorly understood. Here, we interrogate the impact of systemic iron through dietary modulation (control, iron deficiency (ID), and high iron diets), stratified by sex, on tumor iron handling and GBM outcomes utilizing an immune competent (C57BL/6) GBM (GL261) mouse model. Subsequently, we analyzed clinical samples to evaluate translational value. In the preclinical study, we show that iron deficiency decreased survival in males but conferred a slight survival advantage in females, consistent with prior clinical trends. Among circulating iron markers, only ferritin light chain (FTL), but not ferritin heavy chain (FTH) or serum iron, positively correlated with survival in males but not females. In the brain, contralateral iron levels reflected dietary iron status in males but not females, further supporting sex-dependent regulation of local and circulating iron. Notably, tumor iron content remained unchanged in males but was significantly elevated in ID female tumors, complemented by increased transferrin receptor (TfR1) and FTH expression. In clinical GBM samples, we observed non-statistically significant but similar survival trends across varying iron and ferritin levels, suggesting potential translational relevance of our exploratory model. These findings demonstrate that systemic iron availability exerts a sex-specific effect on tumor iron handling, highlighting a critical relationship between systemic and tumor iron regulation in GBM.People with longstanding hip and groin pain (LHGP) are often referred to orthopaedic care. Physical therapist-led interventions are recommended in consensus statements as the first line of treatment, but it is unknown if structured interventions are more effective than usual care. The aim of this trial is to evaluate the effectiveness of a structured physical therapist-led treatment model (HIPSTER) compared with usual care on hip-related quality of life at 4 months for people with LHGP referred to orthopaedic care.
This is a preregistered (clinicaltrials.gov, NCT05853640) study protocol for a double-blinded two-armed pragmatic randomised controlled trial. Patients with LHGP (n=122), referred to the Department of Orthopaedics at a university hospital in Sweden, will be randomised into the HIPSTER model or usual care. The HIPSTER model is a 16-week structured, individualised progressive treatment using exercise therapy and patient education. Usual care consists of a recommendation to contact a physical therapist in primary care. Both groups will undergo standard examinations and a surgical consultation at the Department of Orthopaedics. The primary outcome will be the mean group change in the International Hip Outcome Tool from baseline to 4 months, according to intention-to-treat principles. Secondary outcomes include patient-reported outcomes (such as perceived improvement, psychological factors and physical activity), physical impairment tests and radiographic measures. Additional time points will be 1, 2 and 5 years after baseline. Subgroups of patients will complete semistructured interviews and report additional data on psychosocial variables to provide more information on patient experience as well as determinants of adherence.
The Swedish Ethical Review Authority approved this study (Dnr 202205023–01). The results of this study will be published, regardless of results, in scientific journals and as plain language summaries for participants.
This study aimed to assess construct validity against commonly used patient-reported outcome measures (PROMs), test–retest reliability and responsiveness of seven Dutch-Flemish Patient-Reported Outcomes Measurement Information System (PROMIS) computerised adaptive testing (CATs) in Dutch adults with type 2 diabetes (T2D), and assess their acceptability in healthcare providers and people with T2D.
A cross-sectional observational study in people with T2D and qualitative study involving both people with T2D and healthcare professionals.
Participants with T2D were recruited from the ongoing Hoorn Diabetes Care System cohort in the West-Friesland area of the Netherlands. Additionally, people with T2D and advanced chronic kidney disease were recruited at the outpatient clinics of Amsterdam University Medical Centre and ‘Niercentrum aan de Amstel’, both in the Amsterdam area of the Netherlands. The healthcare professionals involved in the qualitative part were recruited at the Amsterdam University Medical Centre.
314 people with T2D (age 64.0±10.8 years, 63.7% men).
Participants completed seven PROMIS CATs (assessing (1) Physical Function, (2) Pain Interference, (3) Fatigue, (4) Sleep Disturbance, (5) Anxiety, (6) Depression and (7) Ability to Participate in Social Roles and Activities), and PROMs measuring similar constructs. After 2 weeks and 6 months, participants completed the CATs measures again, together with seven Global Rating Scales (GRS) on perceived change in each domain. Construct validity was assessed using Pearson’s correlations. Test–retest reliability was assessed by the intraclass correlation coefficient (ICC). Measurement error was assessed by the standard error of measurement (SEM) and minimal detectable change (MDC). Responsiveness was assessed by correlations between change scores on the PROMIS CAT and GRS. Acceptability was assessed through focus groups and interviews in healthcare providers and people with T2D.
Except for Fatigue, all PROMIS CAT domains demonstrated sufficient construct validity, since ≥75% of the results was in accordance with a priori hypotheses. All seven PROMIS CATs showed sufficient test–retest reliability (ICCs 0.73–0.91). SEM and MDC ranged from 2.1 to 2.7 and from 5.7 to 7.4, respectively. Responsiveness was rated as insufficient in this study design as there was almost no change in participants’ own rating of their health compared with 6 months ago according to a global rating of change.
During the focus groups and interviews, healthcare providers and people with T2D agreed that CATs could serve as a conversation starter in routine care, but should never replace personal consultations with a doctor. If implemented, participants would be willing to spend 15 min to complete the PROMIS CATs.
The PROMIS CATs showed sufficient construct validity and test–retest reliability in most domains in people with T2D. Responsiveness needs to be evaluated in a population with poorer diabetes control or in a study design with longer follow-up. The CATs are well accepted to be used in care to identify relevant topics, but should not replace personal contact with the doctor.
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