The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular ...neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section mns per sect and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity.
Objective To report preliminary experience in using Microporous Polysaccharide Hemospheres (MPH; Medafor, Inc, Minneapolis, Minnesota, USA) for cerebral and dural sinus hemostasis. Methods Absorbable ...hemospheres for hemostasis were used in 10 patients (6 men, 4 women, mean age 56.2 years) undergoing cerebral procedures. The indication was corticosubcortical cerebral hemostasis after resection of meningiomas ( n = 5) and gliomas ( n = 5). In one case, absorbable hemospheres were applied for generalized oozing over the superior sagittal sinus. The surgical technique, time to bleeding control, and associated complications were recorded. Results Effective hemostasis, defined as cessation of oozing bleeding, was achieved no later than 2 minutes after topical agent application in all patients except two, in whom the hemostatic application was repeated. Mean follow-up was 12 months. No patient developed allergic reactions or systemic complications in association with hemostatic absorbable hemospheres. There was no case of cerebral hematoma, swelling, or infection after surgery. Conclusions In this preliminary study, the direct application of absorbable hemospheres helped to control superficial cerebral bleeding, reducing the use of bipolar coagulation and shortening surgical time. Although use of absorbable hemospheres seems to be safe and effective, further investigations and prospective studies with longer follow-up are strongly recommended to arrive at final conclusions.
Purpose
Since 1992, the Centers for Disease Control and Prevention recommends that women of childbearing age consume 400 µg of folic acid per day to reduce the risk of neural tube defects (NTD). It ...has been speculated that both NTD and nervous system tumors (NST) may share common mechanisms of altered development. It examines the association between folic acid supplementation and the risk for childhood NST.
Methods
Incident cases of children with cancer in Spain registered between 2004 and 2006 were identified through the MACAPE Network Group. Tumors were classified as tumors derived from the neuroectoderm (cases) and those with a mesoderm origin (controls). In a second analysis, NST were further divided into central nervous system tumors (CNST) and sympathetic nervous system tumors (SNST). We compared folic acid supplementation between the groups.
Results
Overall, folic acid supplementation any time during pregnancy was similar between cases and controls (odds ratio (OR) = 1.05; 95% confidence interval (CI) 0.92–1.20). However, supplementation before the 21st and 36th days of gestation resulted in significantly lower NST than in children with mesoderm tumors (OR = 0.34; 95% CI 0.17–0.69 and OR = 0.58; 95% CI 0.37–0.91, respectively). Preconceptional intakes of folic acid were also lower in NST although marginally nonsignificant (OR = 0.44; 95% CI 0.10–1.02). When NST were divided into CNST and SNST, significant differences between tumors of mesoderm origin were only found for CNST.
Conclusions
Our results support the hypothesis that folate supplementation reduces the risk of childhood NST, especially CNST. The specific mechanism and cellular role that folate may play in the development of CNST have yet to be elucidated.
Abstract 4393
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterised by loss of motoneurons (mns), and it has no cure. Cell therapy has neurotrophic effects in animal ...models and has been proposed as a disease-modifying treatment. Our aim was twofold: firstly, to assess the safety of intraspinal infusion of bone marrow mononuclear cells (BMNC) and, ultimately, to look for histopathological signs of cellular neurotrophism.
We conducted an open single arm phase I trial. After six months observation, autologous BMNC were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC) and ALS-FRS, MRC and Norris scales were assessed six and three months prior to the transplant and quarterly afterwards for one year. Pathological studies were performed in case of death.
Eleven patients were included. We did not observe any severe transplant-related adverse event but there were 43 non-severe events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were CTCAE grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris or MRC scales was observed. Four patients died on days 359, 378, 808 and 1058 postransplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of montoneurons in the treated compared to the untreated segments (4.2+/−0.8 mns/section and 0.9+/−0.3 mns/section, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits.
This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence of their neurotrophic activity.
No relevant conflicts of interest to declare.
The importance of artificial nutritional therapy is underrecognized, typically being considered an adjunctive rather than a primary therapy. We aimed to evaluate the influence of nutritional therapy ...on mortality in critically ill patients.
This multicenter prospective observational study included adult patients needing artificial nutritional therapy for >48 h if they stayed in one of 38 participating intensive care units for ≥72 h between April and July 2018. Demographic data, comorbidities, diagnoses, nutritional status and therapy (type and details for ≤14 days), and outcomes were registered in a database. Confounders such as disease severity, patient type (e.g., medical, surgical or trauma), and type and duration of nutritional therapy were also included in a multivariate analysis, and hazard ratios (HRs) and 95% confidence intervals (95%CIs) were reported.
We included 639 patients among whom 448 (70.1%) and 191 (29.9%) received enteral and parenteral nutrition, respectively. Mortality was 25.6%, with non-survivors having the following characteristics: older age; more comorbidities; higher Sequential Organ Failure Assessment (SOFA) scores (6.6 ± 3.3 vs 8.4 ± 3.7; P < 0.001); greater nutritional risk (Nutrition Risk in the Critically Ill NUTRIC score: 3.8 ± 2.1 vs 5.2 ± 1.7; P < 0.001); more vasopressor requirements (70.4% vs 83.5%; P=0.001); and more renal replacement therapy (12.2% vs 23.2%; P=0.001). Multivariate analysis showed that older age (HR: 1.023; 95% CI: 1.008–1.038; P=0.003), higher SOFA score (HR: 1.096; 95% CI: 1.036–1.160; P=0.001), higher NUTRIC score (HR: 1.136; 95% CI: 1.025–1.259; P=0.015), requiring parenteral nutrition after starting enteral nutrition (HR: 2.368; 95% CI: 1.168–4.798; P=0.017), and a higher mean Kcal/Kg/day intake (HR: 1.057; 95% CI: 1.015–1.101; P=0.008) were associated with mortality. By contrast, a higher mean protein intake protected against mortality (HR: 0.507; 95% CI: 0.263–0.977; P=0.042).
Old age, higher organ failure scores, and greater nutritional risk appear to be associated with higher mortality. Patients who need parenteral nutrition after starting enteral nutrition may represent a high-risk subgroup for mortality due to illness severity and problems receiving appropriate nutritional therapy. Mean calorie and protein delivery also appeared to influence outcomes.
ClinicaTrials.gov NCT: 03634943.
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Brain abscess. The experience of 30 years Gómez, Joaquín; García-Vázquez, Elisa; Martínez Pérez, Miguel ...
Medicina clínica,
2008-May-24, Letnik:
130, Številka:
19
Journal Article
Recenzirano
The aim of this study was to evaluate epidemiological and clinical aspects of brain abscess (BA) and changes in clinical patterns during the last 30 years.
Observational study of a cohort of ...non-pediatric patients with BA admitted at a 944-bed hospital. Data collection from clinical records was done according to a standard protocol. We analysed epidemiological, clinical and microbiological data and localization as well as changes during a 30 year period divided in 2 equal length phases: 1976-1989 (P1), and 1990-2005 (P2).
108 patients with BA were included (mean age: 45 years; range: 12-86; > 40 years in 42.4% P1, and 71.4% in P2, p < 0.05); 66 patients were treated in P1 and 42 in P2 (annual incidence: 4-5 cases and 2-3 cases per 10(6) population in P1 and P2, respectively). A predisposing condition was identified in 86% cases with statistically significant differences (p < 0.05) in: otitis media (18.2% vs 2.4%); dental infection (3% vs 16.7%); penetrating cranial trauma (16.7% vs 0%); post-neurosurgery (15.1% vs 21.4%), in P1 and P2, respectively; microbiologic diagnosis was made in 76% (no statistical differences P1/P2). Clinical aspects statistically different in P1/P2: severely altered mental status (10.6% vs 0%); vomiting (37.9% vs 21.4%); focal neurological deficits (37.9% vs 71.4%). No statistically significant differences were found in other epidemiological, clinical, radiological, microbiological or outcome characteristics in P1/P2.
In spite of a lower incidence in P2 and certain epidemiological and clinical differences in P1/P2, mortality and relapses rates have not significantly changed in a 30 year period.
Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should ...be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aβ40, Aβ42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aβ40 and Aβ42 levels but not on the Aβ42/Aβ40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aβ40 and Aβ42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.
Abstract
Background
The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With ...tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform.
Methods
Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of
ApoE
4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A − / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors.
Results
Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / − , AD + / − , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89.
Conclusions
Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer’s pathology in cognitively unimpaired subjects.
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