Enhanced glycolysis and GSK3 inactivation promote brain metabolic adaptations following neuronal mitochondrial stress.

We analyzed early brain metabolic adaptations in response to mitochondrial dysfunction in a mouse model of mitochondrial encephalopathy with complex IV deficiency [neuron-specific COX10 knockout (KO)]. In this mouse model, the onset of the mitochondrial defect did not coincide with immediate cell death, suggesting early adaptive metabolic responses to compensate for the energetic deficit. Metabolomic analysis in the KO mice revealed increased levels of glycolytic and pentose phosphate pathway intermediates, amino acids and lysolipids. Glycolysis was modulated by enhanced activity of glycolytic enzymes, and not by their overexpression, suggesting the importance of post-translational modifications in the adaptive response. Glycogen synthase kinase 3 inactivation was the most upstream regulation identified, implying that it is a key event in this adaptive mechanism. Because neurons are thought not to rely on glycolysis for adenosine triphosphate production in normal conditions, our results indicate that neurons still maintain their ability to upregulate this pathway when under mitochondrial respiration stress.

Adjuvant platinum versus capecitabine for residual, invasive, triple-negative breast cancer: Patient-reported outcomes in ECOG-ACRIN EA1131.

BACKGROUND: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). METHODS: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ2 test. RESULTS: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). CONCLUSIONS: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy.

Anilato-Based Coordination Polymers with Slow Relaxation of the Magnetization: Role of the Synthetic Method and Anilato Ligand.

We have prepared and characterized three coordination polymers formulated as [Dy2(C6O4Cl2)3(fma)6] ⋅ 4.5fma (1) and [Dy2(C6O4X2)3(fma)6] ⋅ 4fma ⋅ 2H2O with X=Br (2) and Cl (3), where fma=formamide and C6O4X2 2-=3,6-disubstituted-2,5-dihydroxy-1,4-benzoquinone dianion with X=Cl (chloranilato) and Br (bromanilato). Compounds 1 and 3 are solvates obtained with slow and fast precipitation methods, respectively. Compounds 2 and 3 are isostructural and only differ in the X group of the anilato ligand. The three compounds present (6,3)-gon two-dimensional hexagonal honey-comb structures. Magnetic measurements indicate that the three compounds show slow relaxation of the magnetization at low temperatures when a continuous magnetic field is applied, although with different relaxation times and energy barriers depending on X and the crystallisation molecules. Compounds 1-3 represent the first examples of anilato-based lattices with formamide and field-induced slow relaxation of the magnetization.

Information and vaccine hesitancy: The role of broadband Internet.

We examine the effect of Internet diffusion on the uptake of an important public health intervention: the measles, mumps and rubella (MMR) vaccine. We study England between 2000 and 2011 when Internet diffusion spread rapidly and there was a high profile medical article (falsely) linking the MMR vaccine to autism. OLS estimates suggest Internet diffusion led to an increase in vaccination rates. This result is reversed after allowing for endogeneity of Internet access. The effect of Internet diffusion is sizable. A one standard deviation increase in Internet penetration led to around a 20% decrease in vaccination rates. Localities characterized by higher proportions of high skilled individuals and lower deprivation levels had a larger response to Internet diffusion. These findings are consistent with higher skilled and less-deprived parents responding faster to false information that the vaccine could lead to autism.

Emergency department evaluation of transplanted children with COVID-19.

BACKGROUND: Children usually have an asymptomatic or mild course of SARS-CoV-2 infection, studies in immunocompromised patients have shown a different evolution. The aim of this study was to describe the clinical, laboratory, and radiologic manifestations of pediatric solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients testing positive for SARS-CoV-2. METHODS: A multicenter retrospective, observational descriptive study was conducted in 3 tertiary hospitals in Madrid (Spain) between March 2020 and December 2022. Consecutive patients aged 0-18 attending the corresponding pediatric emergency departments with a positive result in the real-time polymerase chain reaction test or antigenic test to detect SARS-CoV-2 in the nasopharyngeal sample were included. RESULTS: A total of 31 children were included in the study. Sixteen (51.6%) were patients with HSCT and 15 (48.3) were patients with SOT. The median time from transplantation to COVID-19 was 1.2 years (IQR:0.5-5.1). The SOT cohort included liver (n = 4, 12.9%), kidney (n = 4, 12.9%), heart (n = 3, 9.7%), multivisceral (n = 3, 9.7%), and lung (n = 1, 3.2%). Of the 31 patients, only one was asymptomatic. The most common symptom on presentation was fever (76.7%). Abnormalities were seen on chest X-ray in 8 (66.6%) of the 12 patients. There was no significant difference in clinical manifestations, lymphopenia and radiological findings regardless of the type of transplantation or immunosuppression status. Thirteen patients (41.9%) were hospitalized. There were no patient deaths. CONCLUSIONS: In our study, we found that the clinical course and outcome of SOT and HSCT pediatric patients with COVID-19 were generally favorable.

Intravenous immunoglobulin prophylaxis is associated with decreased rate of infection-related hospitalizations in multiple myeloma patients.

This study explored the efficacy of intravenous immunoglobulin (IVIG) prophylaxis in reducing infection-related hospitalizations (IRHs) in MM patients. This was a retrospective study of MM patients who received IVIG at Taussig Cancer Center between July 2009 and July 2021. The primary endpoint was rate of IRHs per patient-year on-IVIG versus off-IVIG. 108 patients were included. There was a significant difference in the primary endpoint of rate of IRHs per patient-year on-IVIG versus off-IVIG in the overall study population (0.81 vs. 1.08; Mean Difference [MD], -0.27; 95% Confidence Interval [CI], -0.57 to 0.03; p value [P] = 0.04). The subgroup of patients with a 1-year period of continuous IVIG (49, 45.3%), the subgroup with standard-risk cytogenetics (54, 50.0%) and the subgroup with 2 or more IRHs (67, 62.0%) all showed a significant reduction in IRHs while on-IVIG versus off-IVIG (0.48 vs. 0.78; MD, -0.30; 95% CI, -0.59 to 0.002; p = 0.03) and (0.65 vs. 1.01; MD, -0.36; 95% CI, -0.71 to -0.01; p = 0.02) and (1.04 vs. 1.43; MD, -0.39; 95% CI, -0.82 to 0.05; p = 0.04) respectively. IVIG showed significant benefit in reducing IRHs in the overall population and in multiple subgroups.

Practical lessons learned from real-world implementation of the molecular classification for endometrial carcinoma.

OBJECTIVES: This study aimed to explore the practical organisational aspects and difficulties in the implementation of the molecular classification of endometrial carcinoma (EC), and to demonstrate its potential impact in prognostic risk group classification. METHODS: We conducted a multicentre, retrospective cohort study of 230 patients with EC diagnosed between 2019 and 2022. Sample processing, clinicopathological, treatment and follow-up data were collected. Molecular classification was obtained by p53 and mismatch repair proteins immunohistochemistry, and POLE next-generation sequencing. RESULTS: Implementation was achieved through centralization of molecular analysis. In practice, it was possible to optimise turnaround times of complete integrative reports for hysterectomy specimens to a median time of 18 workdays. If genetic study was started in endometrial biopsies before surgery, 82.0% were available at the time of multidisciplinary tumour board, compared to 8.4% if performed in hysterectomy. ECs were classified as follows: 37.8% no specific molecular profile, 31.7% p53 abnormal, 24.3% mismatch repair deficient, and 6.1% POLE mutant. Integration of these results with traditional clinicopathologic factors led to a change in prognostic risk group in 15 (6.5%) patients, most being initially allocated to high-intermediate (n = 8) and low (n = 5) risk groups. Eight patients changed to a higher risk, and 7 to a lower risk group, whereas 2 remained in the same group. CONCLUSIONS: Centralization of EC molecular classification is a feasible option for countries with limited resources. Optimization of workflows may be achieved by earlier analysis in biopsies and prioritisation of patients whose results imply changes in risk group classification.

NCCN Guidelines® Insights: Distress Management, Version 2.2023.

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. All patients experience some level of distress associated with a cancer diagnosis and the effects of the disease and its treatment regardless of the stage of disease. Clinically significant levels of distress occur in a subset of patients, and identification and treatment of distress are of utmost importance. The NCCN Distress Management Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights describe updates to the NCCN Distress Thermometer (DT) and Problem List, and to the treatment algorithms for patients with trauma- and stressor-related disorders.

Prevalence of kidney disease of unknown etiology in agricultural workers, Guatemala.

Objectives: To determine the prevalence of kidney disease of unknown etiology in banana, melon, and tomato workers in north-eastern Guatemala, and to evaluate the usefulness of a cystatin C blood test for early detection of renal disease. Methods: This was a cross-sectional, farm-based study of 462 agricultural workers conducted from June to September 2021. Epidemiological and demographic characteristics of the workers were collected through a self-administered questionnaire. Blood samples were obtained to determine glucose, creatinine and cystatin C levels. Anthropometric and clinical data were also recorded. Results: The prevalence of kidney disease of unknown etiology was 3.03% (95% confidence interval (CI): 1.36-4.70%) based on glomerular filtration rate (GFR-EPI) < 60 mL/min/1.73 m2, with a significantly higher prevalence in banana workers (5.67%; 95% CI: 2.16-9.18%) than melon workers (p = 0.009) and tomato workers (p = 0.044). Ten workers (2.16%) had reduced kidney function (GFR-EPI 60-90 mL/min/1.73 m2). The levels of cystatin C showed less variability (coefficient of variation 46.4%) than those of creatinine (coefficient of variation 67.0%), and cystatin C levels in cases with abnormal and reduced kidney function were significantly different from cases with normal kidney function (p < 0.001). Conclusions: Surveillance of the health of active farm workers and improvement of working conditions, such as sun protection, adequate hydration, and sufficient breaks, are recommended. The significant differences in cystatin C levels between cases with abnormal and reduced kidney function and those with normal kidney function suggest that cystatin C could be a useful measure for early detection of renal disease.

Movement and population dispersal of dolphinfish (Coryphaena hippurus) across the Eastern Tropical Pacific inferred from carbon and nitrogen stable isotope analyses.

The dolphinfish (Coryphaena hippurus) is a globally distributed marine predator that supports one of the most important coastal fisheries along the Eastern Tropical Pacific (ETP), but its spatial movements in this area are poorly understood. Stable isotope values (δ13 C and δ15 N) of white muscle from dolphinfish (n = 220) captured at different locations across the ETP (i.e., Mexico, Costa Rica, Ecuador, Peru and oceanic areas) were normalized to copepod baseline stable isotope values to estimate dolphinfish trophic position, movements and population dispersal. Movement or residence patterns were inferred from the difference in δ15 N values (Δ15 Ndolphinfish-copepod ‰) between copepods and dolphinfish muscle. Baseline corrected isotope values (δ13 Cdolphinfish-copepod and δ15 Ndolphinfish-copepod ) of dolphinfish muscle were used to estimate isotopic niche metrics and infer population dispersal across isoscapes. Values of δ13 C and δ15 N differed between juvenile and adult dolphinfish and across the ETP. Trophic position estimates ranged from 3.1 to 6.0 with a mean of 4.6. Adults and juveniles had similar trophic position estimates, whereas isotopic niche areas (SEA ‰2 ) of adults were greater relative to juveniles in every location. Adult dolphinfish showed "moderate movement by some individuals" in all locations based on Δ15 Ndolphinfish-copepod values, except for Costa Rica where adults were classified with "high degree of movement by some individuals" whereas juveniles showed "limited movement" in all areas except Mexico. Population dispersal based on Δ15 Ndolphinfish-copepod values showed "moderate" and "high" dispersal for adults and "no dispersal" for most juveniles, except for Mexico. This study provides insight into potential dolphinfish spatial mobility across an area of interest for multiple nations, which can help to improve stock assessments and management of the species.

Fatigue and endocrine symptoms among women with early breast cancer randomized to endocrine versus chemoendocrine therapy: Results from the TAILORx patient-reported outcomes substudy.

BACKGROUND: TAILORx (Trial Assigning Individualized Options for Treatment) prospectively assessed fatigue and endocrine symptoms among women with early-stage hormone receptor-positive breast cancer and a midrange risk of recurrence who were randomized to endocrine therapy (E) or chemotherapy followed by endocrine therapy (CT+E). METHODS: Participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue, the Patient-Reported Outcomes Measurement Information System-Fatigue Short Form, and the Functional Assessment of Cancer Therapy-Endocrine Symptoms at the baseline and at 3, 6, 12, 24, and 36 months. Linear regression was used to model outcomes on baseline symptoms, treatment, and other factors. RESULTS: Participants (n = 458) in both treatment arms reported greater fatigue and endocrine symptoms at early follow-up in comparison with the baseline. The magnitude of change in fatigue was significantly greater for the CT+E arm than the E arm at 3 and 6 months but not at 12, 24, or 36 months. The CT+E arm reported significantly greater changes in endocrine symptoms from the baseline to 3 months in comparison with the E arm; change scores were not significantly different at later time points. Endocrine symptom trajectories by treatment differed by menopausal status, with the effect larger and increasing for postmenopausal patients. CONCLUSIONS: Adjuvant CT+E was associated with greater increases in fatigue and endocrine symptoms at early time points in comparison with E. These differences lessened over time, and this demonstrated early chemotherapy effects more than long-term ones. Treatment arm differences in endocrine symptoms were more evident in postmenopausal patients. LAY SUMMARY: Participants in TAILORx (Trial Assigning Individualized Options for Treatment) with early-stage hormone receptor-positive breast cancer and an intermediate risk of recurrence were randomly assigned to endocrine or chemoendocrine therapy. Four hundred fifty-eight women reported fatigue and endocrine symptoms at the baseline and at 3, 6, 12, 24, and 36 months. Both groups reported greater symptoms at early follow-up versus the baseline. Increases in fatigue were greater for the chemoendocrine group than the endocrine group at 3 and 6 months but not later. The chemoendocrine group reported greater changes in endocrine symptoms in comparison with the endocrine group at 3 months but not later.

Breast cancer patients' insurance status and residence zip code correlate with early discontinuation of endocrine therapy: An analysis of the ECOG-ACRIN TAILORx trial.

BACKGROUND: Early discontinuation is a substantial barrier to the delivery of endocrine therapies (ETs) and may influence recurrence and survival. The authors investigated the association between early discontinuation of ET and social determinants of health, including insurance coverage and the neighborhood deprivation index (NDI), which was measured on the basis of patients' zip codes, in breast cancer. METHODS: In this retrospective analysis of a prospective randomized clinical trial (Trial Assigning Individualized Options for Treatment), women with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who started ET within a year of study entry were included. Early discontinuation was calculated as stopping ET within 4 years of its start for reasons other than distant recurrence or death via Kaplan-Meier estimates. A Cox proportional hazards joint model was used to analyze the association between early discontinuation of ET and factors such as the study-entry insurance and NDI, with adjustments made for other variables. RESULTS: Of the included 9475 women (mean age, 55.6 years; White race, 84%), 58.0% had private insurance, whereas 11.7% had Medicare, 5.8% had Medicaid, 3.8% were self-pay, and 19.1% were treated at international sites. The early discontinuation rate was 12.3%. Compared with those with private insurance, patients with Medicaid (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.23-1.92) and self-pay patients (HR, 1.65; 95% CI, 1.25-2.17) had higher early discontinuation. Participants with a first-quartile NDI (highest deprivation) had a higher probability of discontinuation than those with a fourth-quartile NDI (lowest deprivation; HR, 1.34; 95% CI, 1.11-1.62). CONCLUSIONS: Patients' insurance and zip code at study entry play roles in adherence to ET, with uninsured and underinsured patients having a high rate of treatment nonadherence. Early identification of patients at risk may improve adherence to therapy. LAY SUMMARY: In this retrospective analysis of 9475 women with breast cancer participating in a clinical trial (Trial Assigning Individualized Options for Treatment), Medicaid and self-pay patients (compared with those with private insurance) and those in the highest quartile of neighborhood deprivation scores (compared with those in the lowest quartile) had a higher probability of early discontinuation of endocrine therapy. These social determinants of health assume larger importance with the expected increase in unemployment rates and loss of insurance coverage in the aftermath of the coronavirus disease 2019 pandemic. Early identification of patients at risk and enrollment in insurance optimization programs may improve the persistence of therapy.

A Low Literacy, Multimedia Health Information Technology Intervention to Enhance Patient-Centered Cancer Care in Safety Net Settings Increased Cancer Knowledge in a Randomized Controlled Trial.

We tested whether a low-literacy-friendly, multimedia information and assessment system used in daily clinical practice enhanced patient-centered care and improved patient outcomes. This was a prospective, parallel-group, randomized controlled trial with 2 arms, CancerHelp-Talking Touchscreen (CancerHelp-TT) versus control, among adults with Stage I-III breast or colorectal cancer receiving chemotherapy and/or radiation therapy in safety net settings. Each patient was assessed for outcomes at 4 timepoints: after starting treatment (baseline), during treatment, immediately after treatment, and at follow-up assessment. The primary outcomes were health beliefs, cancer knowledge, self-efficacy, and satisfaction with communication about cancer and its treatments. Health-related quality of life (HRQOL) was a secondary outcome. A total of 129 patients participated in the study (65 intervention and 64 control), and approximately 50% of these completed the study. Patients randomized to receive the CancerHelp-TT program had a significantly larger increase in their cancer knowledge in comparison to those randomized to the control arm (effect size = .48, P = .05). While effect sizes for differences between randomized groups in self-efficacy, health beliefs, HRQOL, and satisfaction with communication were small (.10-.48), there was a consistent trend that participants in the intervention group showed larger increases over time in all outcomes compared to the control group. The CancerHelp-TT software was favorably rated by intervention participants. The CancerHelp-TT program showed promise to increase vulnerable cancer patients' cancer knowledge and adaptive health beliefs and attitudes. However, vulnerable patients may need additional interventional support in settings outside cancer clinics.

Rasch Analysis of Social Attitude Barriers and Facilitators to Participation for Individuals with Disabilities.

OBJECTIVES: To develop item banks of social attitude barriers and facilitators to participation and validate them with established instruments. DESIGN: We used the Rasch model to identify misfitting items and rating scale problems, calibrate items, and develop KeyForms and short forms. Correlations between the Social Attitude Barriers and Facilitators item banks with the Patient-Reported Outcomes Measurement Information System (PROMIS) Social Health domain and National Institutes of Health Toolbox Emotional Battery Social Relationships domain were computed to evaluate convergent and divergent validity. SETTING: Community-dwelling individuals traveled to 3 academic medical centers for testing. PARTICIPANTS: Participants (N=558) who had a primary impairment of stroke, spinal cord injury, or traumatic brain injury (mean age, 47.0±16.0y) completed 31 social attitude facilitator and 51 barrier items using a 5-point rating scale. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Item banks to measure social attitude barriers and facilitators for individuals with disabilities. RESULTS: After combining the "never" and "rarely" rating scale categories, 30 Facilitator items fit the Rasch model and demonstrated person reliability of 0.93. After collapsing the "never" and "rarely" rating scale categories, 45 Barrier items fit the Rasch model and demonstrated person reliability of 0.95. Ceiling and floor effects were negligible for both item banks. Facilitators and Barriers item banks were negatively correlated, and these banks were moderately correlated with PROMIS and Toolbox measures, providing evidence of convergent and divergent validity. CONCLUSIONS: Findings support the reliability and validity of the Social Attitude Facilitators and Barriers item banks. These item banks allow investigators and clinicians to measure perceptions of social attitudes, providing information that can guide individual interventions to reduce barriers and promote facilitators. Moderate correlations between the Social Attitude banks and PROMIS and Toolbox variables provide support for the measurement and theory of environmental influences on social health and participation.

Feasibility and Preliminary Efficacy of a Bright Light Intervention in Ovarian and Endometrial Cancer Survivors.

BACKGROUND: Cancer-related sleep disturbance is common and can adversely affect physical and mental health. Bright light (BL) therapy is a novel intervention that targets sleep by promoting circadian regulation. Emerging evidence suggests BL can improve sleep disturbance, symptom burden, and health-related quality of life in cancer and other populations; however, this research is limited. The present two-phase pilot study assessed the feasibility and preliminary intended effects of BL therapy on sleep in ovarian and endometrial cancer survivors, and explored biologic and chronobiologic factors that may underlie intervention effects. METHODS: In phase I, focus groups were conducted with 12 survivors and 9 gynecologic oncology clinicians to evaluate and gather feedback about the proposed study. In phase II, a pilot randomized controlled trial was conducted with 18 ovarian or endometrial cancer survivors who were randomized 1:1 to receive 45 min of BL or dim light (DL) for 4 weeks. Participants wore wrist actigraphs; completed sleep diaries and self-report questionnaires; and provided blood, saliva, and urine samples at baseline (T1), post-intervention (T2), and 3-month follow-up (T3). RESULTS: Study procedures were modified according to focus group results. Enrollment, retention, and adherence were all ≥ 80%. Mixed-model ANOVAs demonstrated that the number of nighttime awakenings per actigraphy, and sleep quality and depression per self-report, trended toward improvements in the BL condition compared to the DL condition. These variables improved from T1 to T2 before returning to baseline at T3. Effect sizes were generally medium to large. CONCLUSIONS: Study findings suggest that BL therapy is feasible among ovarian and endometrial cancer survivors. It may be an effective, non-pharmacological approach to reduce sleep disturbance and symptom burden in this population.

Symptom and needs assessment screening in oncology patients: Alternate outreach methods during COVID-19.

Patients with cancer are ideally screened for symptoms, including distress, using patient-reported outcome measures (PROMs). This initiative was developed to ensure patients without access to an electronic portal were screened for distress and related symptoms during the COVID-19 pandemic. Prior to the pandemic, these patients could complete screening in clinic. However, many visits transitioned to telehealth. We implemented a standardized telephone outreach process targeting patients without active electronic portal accounts to improve remote symptom monitoring. Outreach resulted in 172 completed screens, identifying 110 needs for 63 individuals. Twenty-eight patients completed patient portal enrollment. Outreach calls captured a higher percentage of Black patients (34%) and a higher percentage of 61-80 year olds (69%) compared to portal users. Telephone outreach during the pandemic captured data that otherwise would have been missed in elderly and minority patients without electronic patient portal access. Patient engagement is vital to the distress screening process.

The increasing value of eHealth in the delivery of patient-centred cancer care.

The increasing use of eHealth has ushered in a new era of patient-centred cancer care that moves beyond the traditional in-person care model to real-time, dynamic, and technology-assisted assessments and interventions. eHealth has the potential to better the delivery of cancer care through improved patient-provider communication, enhanced symptom and toxicity assessment and management, and optimised patient engagement across the cancer care continuum. In this Review, we provide a brief, narrative appraisal of the peer reviewed literature over the past 10 years related to the uses of patient-centred eHealth to improve cancer care delivery. These uses include the addressal of symptom management, health-related quality of life, and other patient-reported outcomes across cancer care. In addition, we discuss the challenges of, and opportunities for, accessibility, scalability, and implementation of these technologies, important areas for further development, and future research directions.

ATAD3 controls mitochondrial cristae structure in mouse muscle, influencing mtDNA replication and cholesterol levels.

Mutations in the mitochondrial inner membrane ATPase ATAD3A result in neurological syndromes in humans. In mice, the ubiquitous disruption of Atad3 (also known as Atad3a) was embryonic lethal, but a skeletal muscle-specific conditional knockout (KO) was viable. At birth, ATAD3 muscle KO mice had normal weight, but from 2 months onwards they showed progressive motor-impaired coordination and weakness. Loss of ATAD3 caused early and severe mitochondrial structural abnormalities, mitochondrial proliferation and muscle atrophy. There was dramatic reduction in mitochondrial cristae junctions and overall cristae morphology. The lack of mitochondrial cristae was accompanied by a reduction in high molecular weight mitochondrial contact site and cristae organizing system (MICOS) complexes, and to a lesser extent in OPA1. Moreover, muscles lacking ATAD3 showed altered cholesterol metabolism, accumulation of mitochondrial DNA (mtDNA) replication intermediates, progressive mtDNA depletion and deletions. Unexpectedly, decreases in the levels of some OXPHOS components occurred after cristae destabilization, indicating that ATAD3 is not crucial for mitochondrial translation, as previously suggested. Our results show a critical early role of ATAD3 in regulating mitochondrial inner membrane structure, leading to secondary defects in mtDNA replication and complex V and cholesterol levels in postmitotic tissue.This article has an associated First Person interview with the first author of the paper.

Impact of 68Ga-PSMA PET/CT in the treatment of prostate cancer: Initial experience in Spain.

AIM: To evaluate whether positron-emission tomography/computed tomography with 68Ga-PSMA (68Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer (PCa). BACKGROUND: Although 68Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent 68Ga-PSMA PET/CT imaging. MATERIALS AND METHODS: All patients (n = 27) with a histological diagnosis of PCa who underwent 68Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017-2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the 68Ga-PSMA PET/CT were available. RESULTS: Most patients (n = 26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent 68Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall, 68Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests-MRI, CT, or bone scans-performed prior to the 68Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the 68Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study. CONCLUSIONS: 68Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.

Implementing electronic health record-integrated screening of patient-reported symptoms and supportive care needs in a comprehensive cancer center.

BACKGROUND: Oncology practice can be enhanced by the integration of the assessment of patient-reported symptoms and concerns into the electronic health record (EHR) and clinical workflows. METHODS: Adult oncology outpatients (n = 6825) received 38,422 invitations to complete assessments through the EHR patient portal. Patient-Reported Outcomes Measurement Information System computer adaptive tests were administered to assess fatigue, pain interference, physical function, depression, and anxiety. Checklists identified psychosocial, nutritional, and informational needs. In real time, assessment results were populated in the EHR, and clinicians were notified of elevated symptoms and needs. RESULTS: In all, 3521 patients (51.6%) completed 8162 assessments; approximately 55% of the responding patients completed 2 or more within 32 months. Fatigue, pain, anxiety, and depression scores were comparable to those of the general population (approximately 5% of assessments triggered clinical alerts across those domains); mean scores indicated a lower level of physical function (with severe scores prompting alerts in nearly 5% of assessments). More than half of assessments triggered an alert based on patient endorsement of supportive care needs, with the majority of those being nutritional (41.82% of assessments). Patient endorsement of supportive care needs was associated with significantly higher anxiety, depression, fatigue, and pain interference scores and lower physical function scores. Patients who triggered clinical alerts tended to be younger and more recently diagnosed, to have greater comorbidities, and to be a racial/ethnic minority. Patients who triggered clinical alerts had more health care service encounters in the ensuing month. CONCLUSIONS: EHR integration facilitated the assessment and reporting of patient-reported symptoms and needs within routine oncology outpatient care.