Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. National Institute for Health and Care Research.

Objective: To determine whether anatomical and functional brain features relate to key persistent post–concussion symptoms (PPCS) in children recovering from mild traumatic brain injuries (mTBI), and whether such brain indices can predict individual recovery from PPCS.Methods: One hundred and ten children with mixed recovery following mTBI were seen at the concussion clinic at Neurology department Alberta Children’s Hospital. The primary outcome was the Post–Concussion Symptom Inventory (PCSI, parent proxy). Sleep disturbance scores (PCSI subdomain) and the Neurocognition Index (CNS Vital Signs) were also measured longitudinally. PPCS was assessed at 4 weeks postinjury and 8–10 weeks postinjury. Gray matter volumes were assessed using magnetic resonance imaging (MRI) and voxel‐based morphometry at 4 weeks postinjury. Functional connectivity was estimated at the same timepoint using resting‐state MRI. Two complementary machine learning methods were used to assess if the combination of gray matter and functional connectivity indices carried meaningful prognostic information.Results: Higher scores on a composite index of sleep disturbance, including fatigue, were associated with converging decreases in gray matter volume and local functional connectivity in two key nodes of the default mode network: the posterior cingulate cortex and the medial prefrontal cortex. Sleep‐related disturbances also significantly correlated with reductions in functional connectivity between these brain regions. The combination of structural and functional brain indices associated to individual variations in the default mode network accurately predicted clinical outcomes at follow‐up (area under the curve = 0.86).Interpretation: These results highlight that the function–structure profile of core default mode regions underpins sleep‐related problems following mTBI and carries meaningful prognostic information for pediatric concussion recovery.

Persistent post‐concussion symptoms (PCS) in children following a mild traumatic brain injury (mTBI) are a growing public health concern. There is a pressing need to understand the neural underpinning of PCS. Here, we examined whole‐brain functional connectivity from resting‐state fMRI with behavioral assessments in a cohort of 110 children with mTBI. Children with mTBI and controls had similar levels of connectivity. PCS symptoms and behaviors including poor cognition and sleep were associated with connectivity within functional brain networks. The identification of a single “positive‐negative” dimension linking connectivity with behaviors enables better prognosis and stratification toward personalized therapeutic interventions.

The emergence of distributed patterns of neural activity supporting brain functions and behavior can be understood by study of the brain’s low-dimensional topology. Functional neuroimaging demonstrates that brain activity linked to adaptive behavior is constrained to low-dimensional manifolds. In human participants, we tested whether these low-dimensional constraints preserve working memory performance following local neuronal perturbations. We combined multi-session functional magnetic resonance imaging, non-invasive transcranial magnetic stimulation (TMS), and methods translated from the fields of complex systems and computational biology to assess the functional link between changes in local neural activity and the reshaping of task-related low dimensional trajectories of brain activity. We show that specific reconfigurations of low-dimensional trajectories of brain activity sustain effective working memory performance following TMS manipulation of local activity on, but not off, the space traversed by these trajectories. We highlight an association between the multi-scale changes in brain activity underpinning cognitive function.

Persistent post-concussion symptoms (PPCS) following pediatric mild traumatic brain injury (mTBI) are associated with differential changes in cerebral blood flow (CBF). Given its potential as a therapeutic target, we examined CBF changes during recovery in children with PPCS. We hypothesized that CBF would decrease and that such decreases would mirror clinical recovery. In a prospective cohort study, 61 children and adolescents (mean age 14 [standard deviation = 2.6] years; 41% male) with PPCS were imaged with three-dimensional (3D) pseudo-continuous arterial spin-labelled (pCASL) magnetic resonance imaging (MRI) at 4–6 and 8–10 weeks post-injury. Exclusion criteria included any significant past medical history and/or previous concussion within the past 3 months. Twenty-three participants had clinically recovered at the time of the second scan. We found that relative and mean absolute CBF were higher in participants with poor recovery, 44.0 (95% confidence interval [CI]: 43.32, 44.67) than in those with good recovery, 42.19 (95% CI: 41.77, 42.60) mL/min/100 g gray tissue and decreased over time (β = -1.75; p < 0.001). The decrease was greater in those with good recovery (β = 2.29; p < 0.001) and predicted outcome in 77% of children with PPCS (odds ratio [OR] 0.54, 95% CI: 0.36, 0.80; p = 0.002). Future studies are warranted to validate the utility of CBF as a useful predictive biomarker of outcome in PPCS.