Articles: cations.
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The ischemia/reperfusion mechanism is believed to be responsible for parenchymal damage caused by temporary hypoperfusion and worsened by the subsequent attempt of reperfusion. This represents a true challenge for physicians of several fields, including neurosurgeons. A limited number of papers have shed the light on a rare pathologic condition that affects patients experiencing an unexplained neurologic deficit after spine surgery, the so-called "white cord syndrome." This entity is believed to be caused by an "ischemia/reperfusion" injury on the spinal cord, documented by a postoperative intramedullary hyperintensity on T2-weighted magnetic resonance imaging sequences. ⋯ The same neuroradiologic finding can suggest mechanical damage due to inappropriate surgical manipulation. On this purpose, we performed a systematic review of the literature with the aim to identify and analyze all the factors potentially contributing to ischemic/reperfusion damage of the spinal cord that may potentially complicate any spinal surgery, without distinction between cervical or thoracic segments. Finally, we believe that postoperative neurologic deficit after spinal surgery constituting the "white cord syndrome" could be under-reported; both neurosurgeons and patients should be fully aware of this rare but potentially devasting complication burdening cervical and thoracic spine surgery.
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Review
Tau biomarkers in Alzheimer's disease: towards implementation in clinical practice and trials.
Deposition of tau aggregates is a pathological hallmark of Alzheimer's disease that is closely linked both spatially and temporally to emergence of neurodegeneration and manifestation of clinical symptoms. There is an urgent need for accurate PET, CSF, and plasma biomarkers of tau pathology to improve the diagnostic process in clinical practice and the selection of participants and monitoring of treatment effects in trials. ⋯ Innovative second-generation tau-PET tracers with high affinity and selectivity to tau pathology in Alzheimer's disease have enabled detection of tau pathology in medial temporal lobe subregions that are affected in the earliest disease stages. Furthermore, novel but common tau spreading subtypes have been discovered using tau-PET, suggesting much greater interindividual differences in the distribution of tau pathology across the brain than previously assumed. In the CSF biomarker field, novel phosphorylated tau (p-tau) assays have been introduced that better reflect tau tangle load than established CSF biomarkers of tau pathology. The advent of cost-effective and accessible blood-based biomarkers for tau pathophysiology (ie, p-tau181, p-tau217, and p-tau231) might transform the Alzheimer's disease field, as these biomarkers correlate with post-mortem Alzheimer's disease pathology, differentiate Alzheimer's disease from other types of dementia, and predict future progression from normal cognition and mild cognitive impairment to Alzheimer's disease. In controlled investigational settings, improvements in tau-PET and biofluid p-tau markers have led to earlier disease detection, more accurate diagnostic methods, and refinement of prognosis. The anti-tau therapy landscape is rapidly evolving, with multiple ongoing phase 1 and 2 trials of post-translational modification of tau, tau immunotherapy, tau aggregation inhibitors, and targeting production of tau and reduction of intracellular tau levels. Neuroimaging and biofluid tau markers hold potential for optimising such clinical trials by augmenting participant selection, providing evidence of target engagement, and monitoring treatment efficacy. WHERE NEXT?: Major challenges to overcome are the high cost of tau-PET, partial sensitivity to detect early-stage Alzheimer's disease pathology, and off-target tracer binding. Prospective validation studies of biofluid p-tau markers are needed, and assay-related preanalytical and analytical factors need further refinement. Future studies should focus on demonstrating the diagnostic and prognostic accuracy of tau biomarkers-blood-based markers in particular-in non-tertiary settings, such as primary care, which is characterised by a diverse population with medical comorbidities. Large-scale head-to-head studies are needed across different stages of Alzheimer's disease to determine which tau biomarker is optimal in various clinical scenarios, such as early diagnosis, differential diagnosis, and prognosis, and for aspects of clinical trial design, such as proving target engagement, optimising participant selection, and refining monitoring of treatment effects.
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Curr Opin Crit Care · Aug 2022
ReviewIntermittent feeding and circadian rhythm in critical illness.
Circadian rhythms, i.e., periodic oscillations in internal biological processes, modulate metabolic processes such as hormonal signalling, nutrient absorption, and xenobiotic detoxification. Meal timing is a strong entraining cue for peripheral clocks in various organs, and eating out of circadian phases can impair glucose, gastrointestinal, and muscle metabolism. Sleep/wake cycles and circadian rhythms are extremely disrupted during critical illness. Timing of nutritional support may help preserve circadian rhythms and improve post-Intensive Care Unit (ICU) recovery. This review summarises circadian disruptors during ICU admission and evaluates the potential benefits of intermittent feeding on metabolism and circadian rhythms. ⋯ Aligning timing of nutritional intake, physical activity, and/or medication with circadian rhythms are potential strategies to reset peripheral circadian rhythms and may enhance ICU recovery but is not proven beneficial yet. Therefore, selecting intermittent feeding over continuous feeding must be balanced against the pros and cons of clinical practice.
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Sepsis has become the leading cause of death in burn patients. Furthermore, sepsis and septic complications result in significant morbidities and longer hospitalization, which has profound impacts on the healthcare system. Despite this, sepsis in burn patients is surprisingly poorly understood and characterized. ⋯ Applying these definitions, we compared clinical, metabolic, and inflammatory markers in septic and nonseptic burn patients. We found that the Sepsis-3 criteria are the most reliable screening tool used before clinical diagnoses for detecting sepsis trajectories and biochemical patterns. Moreover, we characterized distinct temporal alterations in biomarkers during the pre- and post-septic periods in burn patients, which may be incorporated into future sepsis definitions to improve the accuracy of a sepsis diagnosis in burn patients.