ABSTRACT
INTRODUCTION: While it is recommended that patients with multiple sclerosis (MS) be vaccinated against COVID-19, it is unknown what the vaccine response is in MS patients treated with fingolimod, an agent which modulates the humoral response. We aimed to characterize the immune response to the COVID-19 vaccine in MS patients treated with fingolimod and to explore which factors influenced response. METHOD: We collected the following data from 59 MS patients treated with fingolimod and vaccinated against COVID-19: age, sex, duration of treatment, number of vaccine doses, date of last vaccination, type of vaccine, lymphocyte count, history of COVID-19, and serology to measure the vaccine response. We used Student's t-test and Chi2 test to see whether there was a relationship between these variables and seropositivity. A multivariate logistic regression model was used to identify factors influencing the serology result. A multivariate linear regression model was used to identify factors influencing the antibody titer. RESULTS: Twenty-eight participants (47%) developed a positive serology. Age (P<0.001) and the duration of treatment (P=0.002) were significantly related to seropositivity. Gender (P=0.73), number of vaccinations (P=0.78), lymphocyte count (P=0.46), and the time between the last vaccine dose and blood sampling (P=0.84) were not significant variables. Multivariate analysis using logistic regression (n=59) showed that age (P=0.003, RR = 2.28, 95%CI = 1.28, 4.07) and duration of treatment (P=0.04, RR=1.91, 95%CI=1.04, 3.50) were significantly and independently correlated with COVID serology. Multivariate linear regression analysis of the antibody titer (n=59) found the duration of treatment to be significant (P = 0.015), but not age (P = 0.53). After removing three outliers, age (P = 0.005, RR=6.82, 95%CI=1.66, 27.98) and duration of treatment (P = 0.008, RR=5.12, 95%CI=1.24, 21.03) were significantly correlated with the antibody titer. CONCLUSION: COVID-19 seropositivity was present in 47% of our sample of 59 MS patients on fingolimod. A strong relationship was found between antibody development, age, and duration of treatment, as well as between antibody titer and age and duration of treatment.
Subject(s)
COVID-19 , Multiple Sclerosis , Vaccines , Humans , COVID-19 Vaccines , Fingolimod Hydrochloride , VaccinationABSTRACT
AIM: To investigate the relationships between motor unit action potential amplitudes (MUAPAMP ), muscle cross-sectional area (mCSA) and composition (mEI), per cent myosin heavy chain (%MHC) areas and sex in the vastus lateralis (VL). METHODS: Ten males and 10 females performed a submaximal isometric trapezoid muscle action that included a linearly increasing, steady torque at 40% maximal voluntary contraction, and linearly decreasing segments. Surface electromyographic decomposition techniques were utilized to determine MUAPAMPS in relation to recruitment thresholds (RT). Ultrasound images were taken to quantify muscle mCSA and mEI. Muscle biopsies were collected to calculate %MHC areas. Y-intercepts and slopes were calculated for the MUAPAMP vs RT relationships for each subject. Independent-samples t tests and ANOVA models examined sex-related differences in mCSA, mEI, slopes and y-intercepts for the MUAPAMP vs RT relationships and %MHC areas. Correlations were performed among type IIA and total type II %MHC area, mCSA and the slopes and y-intercepts for the MUAPAMP vs RT relationships. RESULTS: Males exhibited greater slopes for the MUAPAMP vs RT relationships (P = .003), mCSA (P < .001) and type IIA %MHC (P = .011), whereas females had greater type I %MHC area (P = .010) and mEI (P = .024). The mCSA, type IIA and total II %MHC area variables were correlated (P < .001-.015, r = .596-.836) with the slopes from the MUAPAMP vs RT relationships. CONCLUSION: Sex-related differences in mCSA and MUAPAMPS of the higher-threshold MUs were likely the result of larger muscle fibres expressing type II characteristics for males.
Subject(s)
Action Potentials , Myosin Heavy Chains/isolation & purification , Quadriceps Muscle/physiology , Recruitment, Neurophysiological , Sex Characteristics , Female , Humans , Male , Quadriceps Muscle/anatomy & histology , Young AdultABSTRACT
We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.
Subject(s)
Ceruloplasmin/deficiency , Chelation Therapy/methods , Iron , Plasma Exchange/methods , Ceruloplasmin/therapeutic use , Combined Modality Therapy , Humans , Iron Metabolism Disorders/drug therapy , Male , Middle Aged , Neurodegenerative Diseases/drug therapy , PlasmaABSTRACT
This article deals with rhythm in the experiences of infants, focusing in particular on the function of rhythmicity in the baby's sense of being and its continuity. Infants are inevitably subjected to experiences of discontinuity. These experiences are necessary to development, but they expose the child to chaotic experiences when a basic rhythmicity is not ensured. The rhythmicity of childcare experiences gives the illusion of permanence and enables anticipation. This nourishes the basic feeling of security and supports the development of thought. Interactive and intersubjective exchanges must be rhythmic and must be in keeping with the rhythm of the baby, who needs to withdraw regularly from the interaction to internalize the experience of the exchange. Without this retreat, the interaction is over-stimulating and prevents internalization. Object presence/ absence must also be rhythmic, to enable the infant to keep the object alive inside him/ herself. Observation of babies has demonstrated their ability to manage experiences of discontinuity: they are able to sustain a continuous link via their gaze, look for clues indicating the presence of a lost object, search for support in sensations, and fabricate rhythmicity to remain open to the self and the world. The author gives some examples of infant observations that provide evidence of these capacities. One observation shows how a baby defends itself against a discontinuity by actively maintaining a link via his/her gaze. Another example shows an infant holding on to "hard sensations" in order to stay away from "soft" ones, which represent the fragility of the separation experience. This example pertains to a seven-month-old's prelanguage and "prosodic tonicity". The author takes this opportunity to propose the notion of "psychic bisensuality" to describe these two sensation poles, which must be harmoniously articulated to guarantee an inner sense of security. Such repairs of discontinuity are only possible if the experience of discontinuity is not overly disorganizing. For instance, if an object is absent for more than a certain amount of time, it is no longer alive in the infant's mind and despair is inevitable. This prompts us to think carefully about the separation experiences we impose upon babies and their duration. Rhythms of security set in right from the beginning of early childhood, or even in utero. The author gives an example of recourse to inner rhythmicity in an 8 - or 9-month-old baby, which serves to ground the baby's sense of security. In infants, as in each one of us, rhythmicity organizes a foundation of permanence and bridges the gap created by separation. If leaning on sensations and creating neo-rhythms fails to repair the discontinuities, the baby will plunge into experiences of chaos and confusion, as seen, for example, in inconsolability. Even in this latter case, one can find a rhythmicity in the infant's crying, for example, as if the baby didn't want to be separated from the sorrow, a sort of paradoxical companion. Traces of all these primitive defenses can be found in the older child and in adult psychopathology. The importance of rhythmicity is stressed in relation to learning, which involves the experience of otherness and reality, and the rhythmic patterns of engagement and withdrawal support the integration process. The same holds true for the caretaking relationship: rhythmic involvement supports coming together, sharing, and understanding. In all of these situations, the parent, the teacher, the caregiver, must adapt to the child, the pupil, the patient; the external rhythms must fit the internal rhythm of the subject.
Subject(s)
Child Development/physiology , Periodicity , Adult , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Psychology, ChildABSTRACT
The cytolytic protein perforin is a key component of the immune response and is implicated in a number of human pathologies and therapy-induced conditions. A novel series of small molecule inhibitors of perforin function have been developed as potential immunosuppressive agents. The pharmacokinetics and metabolic stability of a series of 16 inhibitors of perforin was evaluated in male CD1 mice following intravenous administration. The compounds were well tolerated 6 h after dosing. After intravenous administration at 5 mg/kg, maximum plasma concentrations ranged from 532 ± 200 to 10,061 ± 12 ng/mL across the series. Plasma concentrations were greater than the concentrations required for in vitro inhibitory activity for 11 of the compounds. Following an initial rapid distribution phase, the elimination half-life values for the series ranged from 0.82 ± 0.25 to 4.38 ± 4.48 h. All compounds in the series were susceptible to oxidative biotransformation. Following incubations with microsomal preparations, a tenfold range in in vitro half-life was observed across the series. The data suggests that oxidative biotransformation was not singularly responsible for clearance of the compounds and no direct relationship between microsomal clearance and plasma clearance was observed. Structural modifications however, do provide some information as to the relative microsomal stability of the compounds, which may be useful for further drug development.
Subject(s)
Immunosuppressive Agents/pharmacokinetics , Perforin/antagonists & inhibitors , Perforin/metabolism , Animals , Drug Evaluation, Preclinical/methods , Male , Mice , Microsomes, Liver/drug effects , Microsomes, Liver/metabolismABSTRACT
AIM: Pneumonectomy is the standard surgery for resectable locally advanced lung cancer. Objectives of this study were: 1) to assess the overall survival; 2) to evaluate the pulmonary and cardiac function impairment; 3) to monitor quality of life (QoL) in a consecutive series of patients undergoing pneumonectomy, defining the potential risk factors of a poor prognosis. METHODS: From January 2003 to March 2010, 71 patients undergoing pneumonectomy for lung cancer or mesothelioma were prospectively enrolled in this study. Twenty-six patients underwent right pneumonectomy (2 of them underwent intrapericardial pneumonectomy), 31 left pneumonectomy (3 of them underwent intrapericardial pneumonectomy), 3 extended pneumonectomy, 3 extrapleural pneumonectomy and 5 patients underwent completion pneumonectomy. Three patients were not included in the study for early postoperative deaths (4.3%). All patients underwent complete preoperative assessment and one year after surgery. QoL was assessed by a questionnaire. RESULTS: One and five-year survival rate was 93% (N.=63) and 20% (N.=14), respectively. Mean values of FEV1 decreased from 2.59±0.75 L to 1.8±0.72 L (P<0.001). One year after surgery all patients showed moderate tricuspid valve insufficiency, PASP significantly higher and right ventricular free wall thickness moderately increased. An increased negative effect was recorded in the QoL scores with P<0.001. Three clinical and surgical parameters were identified as risk or protective factors for the survival outcome. CONCLUSION: Postoperative mortality (4.3%) and five-year survival (20%) after pneumonectomy seem to be satisfactory. Late cardiopulmonary insufficiency is uncommon and acceptable QoL is still achievable.
Subject(s)
Lung Neoplasms/mortality , Lung Neoplasms/surgery , Pneumonectomy , Quality of Life , Female , Heart Function Tests , Humans , Male , Middle Aged , Prospective Studies , Respiratory Function Tests , Risk Factors , Survival Rate , Time FactorsABSTRACT
Stage T4 non small cell lung cancer (NSCLC) includes an heterogeneous group of locally advanced tumors. Results of surgery alone and of chemo and/or radiotherapy are disappointing with 5-year survival rates under 10%. Although palliative chemo-radiotherapy is the treatment of choice in most cases, radical resection has shown prognostic benefit in selected groups of patients with tumor infiltrating Superior Vena Cava, carina, aorta, left atrium and vertebral bodies. Completeness of resection and absence of mediastinal nodal involvement are fundamental conditions for the long-term success of surgery. Increased postoperative 30-day mortality and 90-day mortality rates have been reported up to 8% and 18% respectively. Neoadjuvant therapy, in the last decades, has shown to improve survival of T4 NSCLC patients undergoing surgery and to increase the number of patients suitable for surgical resection. Surgical resection is not indicated in patients with neoplastic pleural effusion since it is generally related to a worse prognosis in such cases. Conversely, patients with T4 tumor due to neoplastic satellite nodule in the same lobe are good surgical candidates. In some studies, these patients show a significant survival advantage after surgical treatment with respect to patients with other types of T4 tumors, when no mediastinal nodal involvement is associated.
Subject(s)
Lung Neoplasms/pathology , Lung Neoplasms/surgery , Humans , Neoplasm Metastasis , Neoplasm Staging , Treatment OutcomeABSTRACT
Postoperative alveolar fistula (AF) associated with pleural cavity (PC) is a serious complication and a therapeutic challenge in thoracic surgery. The purpose of this study was to assess the efficacy of the use of the autologous platelet gel for the treatment of AF and PC. We treated a patient with post lung resection persistent alveolar fistula using a autologous platelet gel, a cellular compose produces at the Division of Immunohaematoligy and Trasfusion. The platelet gel-PRP (Platelet-Rich Plasma) is a biological material made of autologous platelets, extracted from a small amount of the patient's blood, centrifuged at 1100 g for 9 min. The PRP obtained was activated by addition of autologous thrombin and calcium chloride to form a matrix of fibrin (PRFM) thick. The patient presented important air leak after middle lobe wedge resection for solitary lung lesion with standard open decortication for important pleural adhesions post pleuritis. On postoperative day XIII the patient developed a thoracic empyema and consequently underwent a antibiotic pleural irrigation through the chest drainage based on the microbiological analysis of the pleural fluid. After a week we obtained the resolution of the empyema but a residual space remained and air leak persisted. We treated the patient with autologous platelet gel. We administer 7.5 mL of the autologous platelet gel across the chest drainage ever 72 hours for 3 times. After the third application we had the closure of the cavity and the cessation of air leak. Autologous platelet gel is easy to use, safe and inexpensive. It can be considered a valid therapeutic option in selected patients with a alveolar fistula and a lung partial re-expansion. The product consist of a significant amount of cellular components with healing anti-inflammatory an proregenerative properities that permit the body to heal tissue wounds faster and more efficiently. A sterile pleural cavity is fundamental conditions for the final success of the procedure.
Subject(s)
Platelet Transfusion , Pneumonectomy/adverse effects , Pulmonary Alveoli , Respiratory Tract Fistula/etiology , Respiratory Tract Fistula/therapy , Gels , Humans , Male , Middle AgedABSTRACT
OBJECTIVE To assess the feasibility, safety and preliminary efficacy of intra-arterial thrombolysis (IAT) compared with standard intravenous thrombolysis (IVT) for acute ischemic stroke. METHODS Eligible patients with ischemic stroke, who were devoid of contraindications, started IVT within 3 h or IAT as soon as possible within 6 h. Patients were randomized within 3 h of onset to receive either intravenous alteplase, in accordance with the current European labeling, or up to 0.9 mg/kg intra-arterial alteplase (maximum 90 mg), over 60 min into the thrombus, if necessary with mechanical clot disruption and/or retrieval. The purpose of the study was to determine the proportion of favorable outcome at 90 days. Safety endpoints included symptomatic intracranial hemorrhage (SICH), death and other serious adverse events. RESULTS 54 patients (25 IAT) were enrolled. Median time from stroke onset to start to treatment was 3 h 15 min for IAT and 2 h 35 min for IVT (p<0.001). Almost twice as many patients on IAT as those on IVT survived without residual disability (12/25 vs 8/29; OR 3.2; 95% CI 0.9 to 11.4; p=0.067). SICH occurred in 2/25 patients on IAT and in 4/29 on IVT (OR 0.5; CI 0.1 to 3.3; p=0.675). Mortality at day 7 was 5/25 (IAT) compared with 4/29 (IVT) (OR 1.6; CI 0.4 to 6.7; p=0.718). There was no significant difference in the rate of other serious adverse events. CONCLUSIONS Rapid initiation of IAT is a safe and feasible alternative to IVT in acute ischemic stroke.
Subject(s)
Brain Ischemia/drug therapy , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Aged , Brain Ischemia/mortality , Feasibility Studies , Female , Follow-Up Studies , Humans , Infusions, Intra-Arterial , Infusions, Intravenous , Male , Middle Aged , Pilot Projects , Stroke/mortality , Survival Rate/trends , Time Factors , Treatment OutcomeABSTRACT
AIM: Supraventricular tachyarrhythmias, most frequently atrial fibrillation (AF), occur in 8-30% of patients undergoing major pulmonary resection. The aim of this study was to characterize a biochemical marker in order to identify subjects at higher risk of postoperative AF. The authors tested the hypothesis that elevated preoperative plasma levels of N-terminal brain-type natriuretic peptide (NT-pro-BNP) may predict the occurrence of postoperative AF. METHODS: Fifty-five consecutive patients undergoing elective major thoracic surgery were selected. All patients had 12-lead electrocardiogram and transthoracic echocardiographic evaluation at entry. Plasma NT-pro BNP levels were determined both at baseline and at the first postoperative day. Patients were monitored thereafter to detect the occurrence of AF. For statistical analysis, an unpaired Student t test was used to compare continuous variables, chi(2) tests or Fischer exact tests were used for categorical variables, as needed. RESULTS: Eight (14.54%) of the 55 patients developed AF with a peak incidence on postoperative days 2 to 3. Baseline NT-pro-BNP was more than two fold higher in patients who developed AF (506.1+/-108.4 pg/mL versus 197.7+/-54.9 pg/mL; P=0.001). Other relevant clinical and diagnostic parameters were not different in the two groups. Patients with NT-pro-BNP level above the median (113.0 pg/mL) had 8-fold increase risk of postoperative AF. CONCLUSION: A preoperative elevated plasma NT-pro-BNP level was associated with the occurrence of AF in patient undergoing major thoracic surgery. Baseline NT-pro-BNP levels may be proposed as a biochemical marker to detect patients at higher risk of postoperative AF who could benefit from prophylactic therapeutic medication.
Subject(s)
Atrial Fibrillation/blood , Atrial Fibrillation/etiology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Pneumonectomy/adverse effects , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: Short term high dose corticosteroid treatment improves symptoms and short term disability after an acute exacerbation of multiple sclerosis (MS) but it is unknown whether its long-term use can reduce the accumulation of disability. OBJECTIVES: To determine the efficacy and safety of long-term corticosteroid use in MS. SEARCH STRATEGY: We searched the following bibliographic databases: CENTRAL (Issue 1, 2007), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). In an effort to identify further published, unpublished and ongoing trials we searched reference lists and contacted trial authors and one pharmaceutical company. SELECTION CRITERIA: We considered controlled, randomised trials (RCTs), with or without blinding, of long term treatment (i.e. longer than 6 months) of any type of corticosteroid in MS, irrespective of disease course. DATA COLLECTION AND ANALYSIS: Reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Three trials, all classified at high risk of bias, contributed to this review (Miller 1961; BPSM 1995; Zivadinov 2001) resulting in a total of 183 participants (91 treated). Corticosteroid therapy did not reduce the risk of being worse at the end of follow-up (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.26 to 1.02) but there was a substantial heterogeneity between studies (I(2): 78.4%). I. v. periodic high dose methylprednisolone (MP) was associated with a significant reduction in the risk of disability progression at 5 years in relapsing-remitting (RR) MS (OR 0.26, 95% CI 0.10 to 0.66), while oral continuous low dose prednisolone was not associated with any risk reduction in disability progression at 18 months (OR 1.23, 95% CI 0.43 to 3.56). Risk of experiencing at least one exacerbation at end of follow-up was not significantly reduced with corticosteroid treatment (OR 0.36; 95% CI 0.10 to 1.25). Only one study recorded adverse events: in one patient i. v. MP was discontinued after the fourth pulse when he developed acute glomerulonephritis; a second patient was removed from the study after the fifth i. v. MP pulse because of severe osteoporosis. AUTHORS' CONCLUSIONS: There is no enough evidence that long-term corticosteroid treatment delays progression of long term disability in patients with MS. Since one study at high risk of bias showed that the administration of pulsed high dose i. v. MP is associated with a significant reduction in the risk of long term disability progression in patients with RR MS, an adequately powered, high quality RCT is needed to investigate this finding.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Long-Term Care , Multiple Sclerosis/drug therapy , Adrenal Cortex Hormones/adverse effects , Disease Progression , Humans , Methylprednisolone/adverse effects , Methylprednisolone/therapeutic use , Prednisolone/adverse effects , Prednisolone/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
Human GraB (hGraB) preferentially induces apoptosis via Bcl-2-regulated mitochondrial damage but can also directly cleave caspases and caspase substrates in cell-free systems. How hGraB kills cells when it is delivered by cytotoxic lymphocytes (CL) and the contribution of hGraB to CL-induced death is still not clear. We show that primary human natural killer (hNK) cells, which specifically used hGraB to induce target cell death, were able to induce apoptosis of cells whose mitochondria were protected by Bcl-2. Purified hGraB also induced apoptosis of Bcl-2-overexpressing targets but only when delivered at 5- to 10-fold the concentration required to kill cells expressing endogenous Bcl-2. Caspases were critical in this process as inhibition of caspase activity permitted clonogenic survival of Bcl-2-overexpressing cells treated with hGraB or hNK cells but did not protect cells that only expressed endogenous Bcl-2. Our data therefore show that hGraB triggers caspase activation via mitochondria-dependent and mitochondria-independent mechanisms that are activated in a hierarchical manner, and that the combined effects of Bcl-2 and direct caspase inhibition can block cell death induced by hGraB and primary hNK cells.
Subject(s)
Apoptosis , Caspases/metabolism , Granzymes/metabolism , Killer Cells, Natural/enzymology , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Secretory Vesicles/enzymology , Amino Acid Chloromethyl Ketones/pharmacology , Apoptosis/drug effects , Caspase Inhibitors , Cell Culture Techniques , Cells, Cultured , Cysteine Proteinase Inhibitors/pharmacology , Dipeptides/pharmacology , Enzyme Activation , Granzymes/antagonists & inhibitors , Granzymes/genetics , HeLa Cells , Humans , Killer Cells, Natural/drug effects , Mitochondria/enzymology , Mitochondrial Membranes/metabolism , Permeability , Protease Inhibitors/pharmacology , Proto-Oncogene Proteins c-bcl-2/genetics , Secretory Vesicles/drug effects , Time Factors , Transfection , X-Linked Inhibitor of Apoptosis Protein/metabolismABSTRACT
AIM: The aim of this study was to assess the usefulness of a lipid formulation containing a physical mixture of medium (MCT) and long chain triglycerides (LCT) compared with a long chain triglycerides emulsion in patients affected by chronic obstructive pulmonary disease with acute respiratory failure. METHODS: Twenty-four patients requiring mechanical ventilation were randomly selected in 2 groups and received total parenteral nutrition. Twelve patients received a MCT/LCT emulsion (50:50), the others used a 100% LCT emulsion. Nutritional status, metabolic rate, time of ventilatory support and weaning were evaluated. RESULTS: Both groups showed an improvement of all nutritional parameters evaluated; oxygen uptake, carbon dioxide output and respiratory gas exchange ratio were similar in both groups. The duration of mechanical ventilation was not significantly different; however, the time of weaning in the MCT/LCT group was significantly shorter. The longer weaning time in the LCT group patients could be related to vasoactive intermediates deriving from long chain fatty acids. The T-cell subsets, which were evaluated for both groups, showed a significant decrease of T helper-T suppressor ratio in the LCT group. CONCLUSION: MCT/LCT emulsion is an effective lipid supplementation and should be considered the therapy of choice in COPD patients; however, the relationship between lipid emulsions administered and length of weaning requires further investigations.
Subject(s)
Parenteral Nutrition , Pulmonary Disease, Chronic Obstructive/therapy , Respiration, Artificial , Triglycerides/therapeutic use , Aged , Female , Humans , Lymphocyte Count , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Structure-Activity Relationship , T-Lymphocyte Subsets , Triglycerides/chemistryABSTRACT
BACKGROUND: Glycoprotein (GP) IIb-IIIa inhibitors block the final common pathway to platelet aggregation antagonising with receptors that bind fibrinogen molecules forming bridges between adjacent platelets. Thus, GP IIb-IIIa inhibitors could favour endogenous thrombolysis by reducing thrombus growth and prevent thrombus re-formation by competitive inhibition with fibrinogen. Currently used in clinical practice for acute coronary syndromes and percutaneous coronary interventions, they could also be useful for patients with acute ischaemic stroke. OBJECTIVES: To assess efficacy and safety of GP IIb-IIIa inhibitors in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched 31 May 2005). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to June 2005) and EMBASE (1980 to June 2005). In an effort to identify further published, unpublished and ongoing trials we searched reference lists and contacted trial authors and pharmaceutical companies. SELECTION CRITERIA: We aimed to analyse unconfounded randomised controlled trials comparing GP IIb-IIIa inhibitors with placebo in patients with acute ischaemic stroke. Only patients who started the treatment within six hours of stroke onset were included. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Two trials involving 474 patients were included. Only data for 414 patients treated within six hours were considered. Patients were treated with intravenous abciximab or placebo. Treatment with abciximab was associated with a non-significant reduction of death and dependency combined (odds ratio (OR) 0.79; 95% confidence interval (CI) 0.54 to 1.17) and of death alone (OR 0.67; 95% CI 0.36 to 1.25). Treatment with abciximab was associated with a non-significant increase of symptomatic intracranial haemorrhages (OR 4.13; 95% CI 0.86 to 19.67) and of major extracranial haemorrhages (OR 1.51; 95% CI 0.25 to 9.12). AUTHORS' CONCLUSIONS: There is currently not enough evidence from randomised controlled trials regarding the efficacy or safety of GP IIb-IIIa inhibitors therapy in acute ischaemic stroke. Results from ongoing trials will help to understand the risk to benefit ratio of these agents.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunoglobulin Fab Fragments/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Stroke/drug therapy , Abciximab , Brain Ischemia/drug therapy , Humans , Randomized Controlled Trials as TopicABSTRACT
Idiopathic cerebral sinus thrombosis (CST) can cause death and serious neurological disability. It is unknown whether smoking, a major risk factor for arterial stroke, is a risk factor also for CST. This work explored the association between smoking and CST in a hospital-based, multicentric, case-control study. In order to avoid the confounding effect of the different risk factors for CST, we analysed the homogeneous subgroup of oral contraceptive users. We compared the prevalence of smoking in a group of 43 young women with CST (cases), whose oral contraceptive use was the only known risk factor, with a sample of 255 healthy contraceptive users of similar age (controls). The prevalence of smoking in cases and controls was similar (26% vs. 29%). The age and geographic area-adjusted odds ratio was 0.9; 95% confidence interval, 0.4-1.8; p=0.7. Smoking in oral contraceptive users does not appear to be associated with CST.
Subject(s)
Contraceptives, Oral/adverse effects , Risk , Sinus Thrombosis, Intracranial/chemically induced , Smoking/epidemiology , Adolescent , Adult , Case-Control Studies , Female , Humans , Interviews as Topic/methods , Middle Aged , Odds Ratio , Retrospective Studies , Risk Factors , Sinus Thrombosis, Intracranial/epidemiologyABSTRACT
BACKGROUND: Lung transplantation is a robust therapeutic option to treat patients with cystic fibrosis. PATIENTS AND METHODS: Since 1996, 109 patients with cystic fibrosis were accepted onto our waiting list with 58 bilateral sequential lung transplants performed in 56 patients and two patients retransplanted for obliterative bronchiolitis syndrome. RESULTS: Preoperative mean FEV(1) was 0.64 L/s, mean PaO(2) with supplemental oxygen was 56 mm Hg, and the mean 6-minute walking test was 320 m. Transplantation was performed through a "clam shell incision" in the first 29 patients and via bilateral anterolateral thoracotomies without sternal division in the remaining patients. Cardiopulmonary bypass was required in 14 patients. In 21 patients the donor lungs had to be trimmed by wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Eleven patients were extubated in the operating room immediately after the procedure. Hospital mortality of 13.8% was related to infection (n = 5), primary graft failure (n = 2), and myocardial infarction (n = 1). Acute rejection episodes occurred 1.6 times per patient/year; lower respiratory tract infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV(1) increased to 82% at 1 year after operation. The 5-year survival rate was 61%. A cyclosporine-based immunosuppressive regimen was initially employed in all patients; 24 were subsequently switched to tacrolimus because of central nervous system toxicity, cyclosporine-related myopathy, or renal failure, obliterative bronchiolitis syndrome, gingival hyperplasia, or hypertrichosis. Ten patients were subsequently switched to sirolimus. Freedom from bronchiolitis obliterans at 5 years was 60%. CONCLUSIONS: Our results confirm that bilateral sequential lung transplantation is a robust therapeutic option for patients with cystic fibrosis.
Subject(s)
Cystic Fibrosis/surgery , Lung Transplantation/physiology , Cystic Fibrosis/physiopathology , Follow-Up Studies , Forced Expiratory Volume , Humans , Lung Transplantation/mortality , Oxygen/blood , Partial Pressure , Postoperative Complications/classification , Postoperative Complications/epidemiology , Reoperation , Retrospective Studies , Survival Analysis , Time FactorsABSTRACT
BACKGROUND: Treatment of cerebral sinus thrombosis with thrombolytics has been reported in cases with a deteriorating clinical course despite anticoagulant therapy. The rationale of this treatment is to promote rapid recanalisation of the occluded sinus. OBJECTIVES: To review the available evidence on the efficacy and safety of thrombolysis in confirmed cerebral sinus thrombosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), and reference lists of all relevant publications. SELECTION CRITERIA: We aimed to analyse separately unconfounded randomised controlled trials comparing thrombolytic agent with placebo, or thrombolytic agent with antithrombotic therapy, or thrombolytic agent and antithrombotic with antithrombotic alone, in patients with dural sinus thrombosis (confirmed by MR venography, intra-arterial venography or CT venography). DATA COLLECTION AND ANALYSIS: Two groups of reviewers independently applied the inclusion criteria. MAIN RESULTS: No randomised controlled trials were found. REVIEWER'S CONCLUSIONS: There is currently no available evidence from randomised controlled trials regarding the efficacy or safety of thrombolytic therapy in dural sinus thrombosis. A randomised controlled trial is justified to test this therapy especially in patients predicted to have a poor prognosis.
Subject(s)
Cerebral Veins , Cranial Sinuses , Sinus Thrombosis, Intracranial/drug therapy , Thrombolytic Therapy , Venous Thrombosis/drug therapy , HumansABSTRACT
BACKGROUND: Gangliosides may have a protective effect on the central and peripheral nervous systems. OBJECTIVES: The objective of this review was to assess the effect of exogenous gangliosides in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched: May 2001) and contacted drug companies and main investigators of included trials. SELECTION CRITERIA: Randomised trials of gangliosides compared with placebo or standard treatment in people with definite or presumed ischaemic stroke. Trials were included if people were randomised within 15 days of symptom onset and if mortality data were available. DATA COLLECTION AND ANALYSIS: One reviewer applied the inclusion criteria. Two reviewers independently extracted the data. Trial quality was assessed. MAIN RESULTS: Twelve trials involving 2265 people were included. All the trials tested purified monosialoganglioside GM1. Only three trials described the randomisation procedure. Follow-up was between 15 to 180 days. Death at the end of follow-up showed no significant difference (odds ratio 0.91, 95% confidence interval 0.73 to 1.13). There was no difference shown between early (within 48 hours) and delayed treatment. For disability, three trials did not show any improvement in Barthel index score with gangliosides (weighted mean difference 2.1; 95% confidence interval -4.8 to 8.9). In two trials, eight patients experienced adverse effects that led to discontinuation of ganglioside treatment, seven had skin reactions and one developed Guillain-Barré syndrome. REVIEWER'S CONCLUSIONS: There is not enough evidence to conclude that gangliosides are beneficial in acute stroke. Caution is warranted because of reports of sporadic cases of Guillain-Barré syndrome after ganglioside therapy.
Subject(s)
Gangliosides/therapeutic use , Stroke/drug therapy , Acute Disease , Brain Ischemia/drug therapy , G(M1) Ganglioside/therapeutic use , HumansABSTRACT
BACKGROUND: The use of thrombolytic therapy for acute ischemic stroke is still controversial. A major problem is balancing the improvement in functional ability against the risk of early death from cerebral hemorrhage. Our aim was to assess whether patients who have had a stroke, and their proxies, would give consent to thrombolysis if this therapy were introduced into clinical practice for acute ischemic stroke in Italy. METHODS: A 10-item questionnaire was administered by personnel not directly involved in the care of patients in 12 Italian hospitals. Interviews were carried out with at least 10 consecutive stroke inpatients per center in the postacute phase and to their proxies. RESULTS: There were 685 responders (377 female), median age 58 years (range 18-98); 332 were patients and 353 proxies. Responders were representative of the Italian population as a whole as regards mean age and sex, education and marital status; 59% of responders (95% confidence interval 55-62%) would agree to thrombolysis in the case of stroke. There was more uncertainty among proxies than patients, especially when the decision had to be taken for a relative (41 vs. 17% could not decide, p < 0.001). The preference for thrombolysis was higher among more educated people (p = 0.001) and was not influenced by sex, age and marital status. Overall, 81% of responders would prefer to risk dying rather than remain severely disabled. CONCLUSION: Thrombolytic therapy is feasible in Italy as there is ample willingness to trade off a better functional outcome with a higher risk of death. Education is the main sociodemographic determinant of independent decision-making, as only those with an adequate cultural level are able to discriminate between one treatment option and another. The proxy's uncertainty about how to interpret a patient's preference regarding consent to thrombolytic therapy should be tackled, since proxies play a key role in making patients' preferences known in case of incompetence after an acute stroke.