The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)
BackgroundThe diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.ObjectiveTo analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.MethodsRetrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).ResultsSeropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.ConclusionThis study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.
Low-density lipoprotein (LDL) apheresis is an extracorporeal modality to lower LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a recently introduced whole-blood perfusion column (DALI) adsorbs lipoproteins directly from whole blood. We investigated the efficacy and safety of a new whole-blood LDL apheresis system (Liposorber D) in 10 patients with severe hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean reduction in LDL cholesterol and lipoprotein(a) was 62.2 +/- 11.5% and 55.6 +/- 16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered, the reductions were 58.0 +/- 10.9 and 55.3 +/- 10.9%, respectively (P < 0.01), while high-density lipoprotein (HDL) cholesterol did not change significantly. Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension were observed; however, LDL apheresis could be continued in each case. In conclusion, the new whole-blood LDL apheresis with Liposorber D is a safe, simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in cardiovascular high-risk patients.
Aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) is a rare but often severe autoimmune disease with median onset around 40 years of age. We report characteristics of three very-late-onset NMOSD (including complete NMO) patients >75 years of age, in whom this diagnosis initially seemed unlikely because of their age and age-associated concomitant diseases, and briefly review the literature. All three patients, aged 79, 82 and 88 years, presented with a spinal cord syndrome as the first clinical manifestation of AQP4-Ab-positive NMOSD. They all had severe relapses unless immunosuppressive therapy was initiated, and one untreated patient died of a fatal NMOSD course. Two patients developed side effects of immunosuppression. We conclude that a first manifestation of NMOSD should be considered even in patients beyond the age of 75 years with a compatible syndrome, especially longitudinally extensive myelitis. Early diagnosis and treatment are feasible and highly relevant. Special attention is warranted in the elderly to recognize adverse effects of immunosuppressive therapies as early as possible.
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