Sedation per se can result in positive items of both CAM-ICU and ICDSC, and therefore in a diagnosis of delirium. Consequently, apparent prevalence of delirium is dependent on how a depressed level of consciousness after sedation stop is interpreted (delirium vs persisting sedation). We suggest that any reports on delirium using these assessment tools should be stratified for a sedation score during the assessment.
Interleukin-6 (IL-6), a major cytokine with diverse effects on cells mainly of the immune and hematopoietic systems, has been linked to several neurological disorders such as acquired immune deficiency syndrome dementia, multiple sclerosis, and Alzheimer's disease. Central nervous system (CNS)-specific expression of IL-6 caused neurodegeneration, massive gliosis, and vascular proliferation in transgenic mice. However, the effects of systemically circulating IL-6 and its receptor IL-6Ralpha on the CNS are unknown. IL-6Ralpha is the specific component of the IL-6 receptor system and hence an important co-factor of IL-6. IL-6Ralpha is bioactive in a membrane-bound and in a soluble (s) form. We investigated the effects of systemically elevated levels of either human IL-6 or human sIL-6Ralpha or both on the CNS of transgenic mice. Although IL-6 and sIL-6Ralpha single transgenic mice were free of neurological disease, IL-6/sIL-6Ralpha double-transgenic mice showed neurological signs, such as tremor, gait abnormalities, and paresis. However, these mice also frequently showed prominent general weakness probably because of the systemic effects of IL-6/IL-6Ralpha such as liver damage and plasmacytomas. IL-6/sIL-6Ralpha transgenic mice exhibited massive reactive gliosis. Lack of signs of neuronal breakdown versus ample astrogliosis suggested that astrocytes were selectively affected in these mice. There was neither vascular proliferation nor inflammatory infiltration. Ultrastructural analysis revealed blood-brain barrier (BBB) changes manifested by hydropic astrocytic end-feet. However, albumin immunohistochemistry did not reveal major BBB leakage. Our results indicate that increased and constitutive systemic expression of IL-6 together with its soluble receptor sIL-6Ralpha is less harmful to the brain than to other organs. The BBB remains primarily intact. IL-6/IL-6Ralpha, however, might be directly responsible for the selective activation of astrocytes.
SummaryThis 5 year observational multicentre study conducted in the Nord Italian Transplant programme area evaluated outcomes in patients receiving kidneys from donors over 60 years allocated according to a combined clinical and histological algorithm. Low-risk donors 60-69 years without risk factors were allocated to single kidney transplant (LR-SKT) based on clinical criteria. Biopsy was performed in donors over 70 years or 60-69 years with risk factors, allocated to Single (HR-SKT) or Dual kidney transplant (HR-DKT) according to the severity of histological damage. Forty HR-DKTs, 41 HR-SKTs and 234 LR-SKTs were evaluated. Baseline differences generally reflected stratification and allocation criteria. Patient and graft (death censored) survival were 90% and 92% for HR-DKT, 85% and 89% for HR-SKT, 88% and 87% for LR-SKT. The algorithm appeared userfriendly in daily practice and was safe and efficient, as demonstrated by satisfactory outcomes in all groups at 5 years. Clinical criteria performed well in low-risk donors. The excellent outcomes observed in DKTs call for fine-tuning of cut-off scores for allocation to DKT or SKT in high-risk patients.
This report emphasizes that transplant-acquired WNV neuroinvasive disease can be particularly severe. We suggest that pre-procurement screening of organ donors by testing blood with both WNV IgM capture ELISA and a sensitive nucleic acid testing should be adopted during the transmission season in the present Italian epidemiological setting.
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