Uppsala University Hospital (Swedish: Akademiska sjukhuset, often referred to colloquially as "Akademiska" or "Ackis") in Uppsala, Sweden, is a teaching hospital for the Uppsala University Faculty of Medicine and the Nursing School. Uppsala University Hospital is owned and operated by the Uppsala County Council in cooperation with the university and serves, together with Enköping hospital in Enköping, as the primary hospitals for Uppsala County. It also fills the function of a tertiary referral hospital for the Uppsala/Örebro health care region and, for certain specialities, a tertiary referral hospital for the entire country of Sweden.
Previous studies from our laboratory showed that topical application of growth hormone (GH) induced neuroprotection 5 h after spinal cord injury (SCI) in a rat model. Since nanodelivery of drugs exerts superior neuroprotective effects, a possibility exists that nanodelivery of GH will induce long-term neuroprotection after a focal SCI. SCI induces GH deficiency that is coupled with insulin-like growth factor-1 (IGF-1) reduction in the plasma. Thus, an exogenous supplement of GH in SCI may enhance the IGF-1 levels in the cord and induce neuroprotection. In the present investigation, we delivered TiO2-nanowired growth hormone (NWGH) after a longitudinal incision of the right dorsal horn at the T10-11 segments in anesthetized rats and compared the results with normal GH therapy on IGF-1 and GH contents in the plasma and in the cord in relation to blood-spinal cord barrier (BSCB) disruption, edema formation, and neuronal injuries. Our results showed a progressive decline in IGF-1 and GH contents in the plasma and the T9 and T12 segments of the cord 12 and 24 h after SCI. Marked increase in the BSCB breakdown, as revealed by extravasation of Evans blue and radioiodine, was seen at these time points after SCI in association with edema and neuronal injuries. Administration of NWGH markedly enhanced the IGF-1 levels and GH contents in plasma and cord after SCI, whereas normal GH was unable to enhance IGF-1 or GH levels 12 or 24 h after SCI. Interestingly, NWGH was also able to reduce BSCB disruption, edema formation, and neuronal injuries after trauma. On the other hand, normal GH was ineffective on these parameters at all time points examined. Taken together, our results are the first to demonstrate that NWGH is quite effective in enhancing IGF-1 and GH levels in the cord and plasma that may be crucial in reducing pathophysiology of SCI.
Accurate evaluation of kidney function is vital in the pediatric intensive care unit (PICU), where even small changes in cystatin C and creatinine concentrations can affect clinical decision-making. Diurnal patterns in renal biomarkers have been reported in adults, but their relevance in critically ill children remains unclear. Understanding whether sampling time contributes to biological variability is essential for reliable interpretation of kidney function tests. This retrospective study included 8619 cystatin C and 9314 creatinine results collected in a tertiary PICU between April 2014 and September 2025. The hourly distribution of sampling and hourly biomarker percentiles (0.10, 0.25, and 0.50) were evaluated across the 24-h cycle. Diurnal variation was quantified using coefficients of variation (CVs). Sampling was strongly clustered in the early morning, with 38.6
Abstract Background and Purpose Magnetic resonance imaging (MRI) is essential in assessing proximal hamstring avulsions (PHA), where tendon retraction is a key pathological consequence. Beyond its diagnostic role, MRI may also provide prognostic information on subsequent muscle degeneration. This study aimed to determine whether pre-treatment MRI findings, particularly tendon retraction, predict later muscle degeneration and clinical outcomes in nonoperatively treated PHA patients. Methods This study is a post hoc analysis of nonoperatively treated patients (n = 95) with complete proximal hamstring avulsions from the Proximal Hamstring Avulsion Clinical Trial (PHACT). Diagnostic MRIs were reassessed for tendon retraction, Wood classification, number of tendons avulsed, and hematoma size. The primary outcome was muscle degeneration, defined by the loss of lean muscle volume (LMV) and an increase in muscle fat fraction (MFF) quantified by DIXON MRI at 24 months. The secondary outcome was maximum hamstring muscle isometric force at 24 months. Outcome data was expressed as the limb symmetry index (LSI), which was the measurement of the injured hamstring expressed as a percentage of measurement of the uninjured hamstring. Linear regression was used to analyze the association between diagnostic MRI measurements, patient factors, and LSIs for LMV, MFF, and maximum isometric force. Results The median (IQR) LSIs of the LMV, MFF and maximum strength were 78% (67.2, 87.1), 139% (124.5, 166.8), and 84% (75.4, 94.0), respectively, at 24-month follow-up. A multivariate linear regression model including tendon retraction, age, sex, hematoma size and whether the dominant limb was injured explained 48%, 48% and 23% of the variance in the LSIs of LMV, MFF and maximum force, respectively. Tendon retraction was the strongest explanatory factor for the variance of muscle degeneration observed in patients with nonoperatively treated PHA. Interpretation Greater initial tendon retraction is associated with increased muscle atrophy and fat infiltration in the hamstring muscles in patients with nonoperatively treated PHA. Trial registration: NCT03311997.
Supplemental Digital Content is Available in the Text.Real-world evidence suggests that higher educational level and employment are associated with a better outcome in patients treated with spinal cord stimulation. Introduction:Despite advancements in implanted hardware and development of novel stimulation paradigms in Spinal Cord Stimulation (SCS), real world evidence suggests a large variation in patient reported outcomes and a proportion of patients are later explanted due to loss of analgesia. Possible predictors for outcome have been explored in smaller short-term evaluations, but few clinically applicable robust measures for long term outcome have emerged.Methods:We performed a comprehensive retrospective study based on an assembled patient-level aggregated database from multiple local and national registries in Sweden. Variables associated with risk of explantation (due to insufficient analgesia) and analgesic effect was analyzed using a Cox regression analysis and an ordered logit regression model, respectively.Results:We found the accumulated risk of explantation due to loss of analgesia to be 10% and 21% at two and ten years follow up, respectively. The use of 10 kHz spinal cord stimulation (compared with Tonic waveform; p = 0.003), and being 60 years or older (reference 18-40 years; p = 0.003) were associated with an increased risk of explantation.At a mean follow up at 1 year, 48% of patients reported a pain intensity reduction from baseline of at least 30%. Secondary (p = 0.030) and post-secondary (p = 0.001) education (compared with primary education) was associated with an increased probability of successful patient reported outcomes.Results:We found the accumulated risk of explantation due to loss of analgesia to be 10% and 21% at two and ten years follow up, respectively. The use of 10 kHz spinal cord stimulation (compared with Tonic waveform; p = 0.003), and being 60 years or older (reference 18-40 years; p = 0.003) were associated with an increased risk of explantation.At a mean follow up at 1 year, 48% of patients reported a pain intensity reduction from baseline of at least 30%. Secondary (p = 0.030) and post-secondary (p = 0.001) education (compared with primary education) was associated with an increased probability of successful patient reported outcomes.Conclusion:This study suggests that a higher educational level and being employed are associated with successful treatment outcome in patients with chronic pain treated with SCS in Sweden.
Triple-negative breast cancer (TNBC) is frequently associated with metastatic relapse, even at an early stage1. Here we assessed an individualized neoantigen mRNA vaccine in 14 patients with TNBC following surgery and after neoadjuvant or adjuvant therapy. In peripheral blood of nearly all patients, high-magnitude, vaccine-induced, mostly de novo T cell responses to multiple neoantigens were detected that remained functional for several years. Characterization of individual patients revealed that a large proportion of these T cells developed into two subsets: a late-differentiated phenotype with markers indicative of 'ready-to-act' cytotoxic effector T cells, and T cells with a stem cell-like memory phenotype. Eleven patients remained relapse-free for up to six years post-vaccination. Recurrence occurred in three patients: the individual with the weakest vaccine-induced T cell response relapsed, but achieved complete remission on subsequent anti-PD-1 therapy; another patient had a tumour with low major histocompatibility complex (MHC) class I expression with MHC class I-deficient cells growing out under vaccination; and the third patient was BRCA-positive and had a recurrence from a genetically distinct primary tumour. These findings demonstrate the feasibility of individualized RNA vaccines in TNBC, document persistence of vaccine-induced, functional neoantigen-specific T cells and provide insights into possible immune escape mechanisms that will guide future approaches.
