TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis

Background and Purpose

Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema.

Methods

We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC).

Results

Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63–0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61–0.73).

Conclusions

Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis.

     

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.     

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

Background

Growing evidence indicates that oxidative stress can be a primary cause of male infertility. Non-enzymatic antioxidants play an important protective role against oxidative damages and lipid peroxidation. Human seminal plasma is a natural reservoir of antioxidants. The aim of this study was to determine glutathione (GSH) concentrations, trace element levels (zinc and selenium) and the lipid peroxidation end product, malondialdehyde (MDA), in the seminal plasma of men with different fertility potentials.

Methods

Semen samples from 60 fertile men (normozoospermics) and 190 infertile patients (74 asthenozoospermics, 56 oligozoospermics, and 60 teratozoospermics) were analyzed for physical and biochemical parameters. Zinc (Zn) and selenium (Se) levels were estimated by atomic absorption spectrophotometry. Total GSH (GSHt), oxidized GSH (GSSG), reduced GSH (GSHr) and MDA concentrations were measured spectrophotometrically.

Results

Zn and Se concentrations in seminal plasma of normozoospermics were more elevated than the three abnormal groups. Nevertheless, only the Zn showed significant differences. On the other hand, Zn showed positive and significant correlations with sperm motility (P = 0.03, r = 0.29) and count (P < 0.01, r = 0.49); however Se was significantly correlated only with sperm motility (P < 0.01, r = 0.36). GSHt, GSSG and GSHr were significantly higher in normozoospermics than in abnormal groups. We noted a significant association between seminal GSHt and sperm motility (P = 0.03). GSSG was highly correlated to sperm motility (P < 0.001) and negatively associated to abnormal morphology (P < 0.001). GSHr was significantly associated to total sperm motility (P < 0.001) and sperm count (P = 0.01). MDA levels were significantly higher in the three abnormal groups than in normozoospermics. Rates of seminal MDA were negatively associated to sperm motility (P < 0.01; r = -0.24) and sperm concentration (P = 0.003; r = -0.35) Meanwhile, there is a positive correlation between seminal lipid peroxidation and the percentage of abnormal morphology (P = 0.008).

Conclusions

This report revealed that decreased seminal GSH and trace element deficiencies are implicated in low sperm quality and may be an important indirect biomarker of idiopathic male infertility. Our results sustain that the evaluation of seminal antioxidant status in infertile men is necessary and can be helpful in fertility assessment from early stages.     

Nutritional problems, overhydration and the association with quality of life in elderly dialysis patients

Purpose

The aim of this pilot study was to describe the hydration and nutritional status of a cohort of elderly dialysis patients and to explore the association between these parameters and the quality of life (QoL).

Methods

All patients over 75?years of age being in chronic dialysis by January 2008 at 3 dialysis units (n?=?34) were asked to participate in this pilot study, 24 patients were entered. Hydration status was assessed by bioimpedance spectroscopy (BIS) and nutritional status by the subjective global assessment (SGA), BIS, anthropometric measures and biochemical parameters. Based on these assessments the patients were classified as being cachectic or not according to newly defined criteria. QoL was measured using the SF-36.

Results

The results showed cachexia in 6 (25?%), 37.5?% had a body mass index below 24, whereas according to SGA 91?% were malnourished. BIS showed low lean tissue index in 46?% and overhydration in 35?% of the patients. Compared to non-cachectic and normohydrated, cachectic and overhydrated patients reported consistently poorer QoL. For cachectic patients, the differences were clinically significant for all SF-36. BIS was easily applicable when used before dialysis.

Conclusions

The high frequency of nutritional deficits in this study calls for more attention to nutritional status in elderly dialysis patients. There is a need for a general agreement on how nutritional status should be assessed and reported, both in clinics and in research.     

Doppler‐guided haemorrhoidal artery ligation in patients with Crohn’s disease

Aim: The outcome of Doppler‐guided haemorrhoidal artery ligation (DGHAL) was assessed in patients with Crohn’s disease (CD) suffering from grade III haemorrhoids. Method: A retrospective study was carried out of patients with CD and symptomatic Grade III haemorrhoids treated by DGHAL. Perioperative and follow‐up data were retrieved from our database of patients undergoing DGHAL. Results: The study included seven men and six women. The mean age was 34 years old. All had CD without anorectal involvement. The median duration of haemorrhoidal symptoms was 6.3 years. There was no mortality, new incontinence, faecal impaction, urinary retention, abscess formation or persistent pain following the procedure. Mean pain score based on a visual analogue scale (VAS) decreased from 2.4 at 24 h postoperatively to 1.6 on the seventh postoperative day. All patients had completely recovered by the third postoperative day. At 18 months, three (77%) of the patients were asymptomatic and three had recurrent symptoms. Conclusion: Doppler‐guided haemorrhoidal artery ligation is safe and effective in treating Grade III haemorrhoids in patients with CD without rectal involvement.     

Aortic valve replacement for aortic regurgitation and stenosis, in patients with severe left ventricular dysfunction.

OBJECTIVE: Aortic valve replacement for aortic valve stenosis (AS) and regurgitation (AR) in patients with severe left ventricular (LV) dysfunction contains an increased risk. Few data are available on the outcome of such patients. METHODS: Fifty-five consecutive patients with severe LV dysfunction (ejection fraction, EF; <30%) and aortic valve replacement for AS (n=35) or AR (n=20) were investigated between 1994 and 2001. EF was 25+/-5%, mean transvalvular gradient 26+/-6mmHg (AS), aortic valve area 0.66+/-0.18cm(2) (AS), cardiac index (CI) 2.4+/-0.9l/min/m(2), enddiastolic LV diameter (LVEDD) 64+/-8mm and endsystolic LV diameters (LVESD) was 55+/-3mm. Ninety percent of patients were in New York Heart Association (NYHA) functional class III/IV at admission to the hospital. Concomitant coronary artery bypass grafts (CABG) were performed in 14 patients. Follow-up examinations including chest X-ray, echocardiography, exercise testing, were performed among survivors. RESULTS: The survival rates for AS were: 1-year 76%, 2-year 68.8%, 5-year 64.2%; for AR: 1-year 94.4%, 2-year 86.5%, 5-year 74.2%. NYHA functional class improved from 90% in class III/IV to 45 (AR group) and 24% (AS group) at follow-up (P<0.02). The LVEDD decreased to 54+/-8mm after 1 year. The EF improved to 38+/-4 (AR group) and 40+/-5% (AS group) at follow-up. CONCLUSIONS: Despite severe LV dysfunction, increased 1-year mortality especially in the AS group, aortic valve replacement was associated with improved functional status, symptoms and EF in both groups and in most patients. We, therefore, conclude that aortic valve replacement in patients with severe LV dysfunction can be performed with acceptable risk.     

Intrathecal coadministration of D-APV and morphine is maximally effective in a rat experimental pancreatitis model

BACKGROUND: Many studies have demonstrated that either glutamate -methyl-d-aspartate (NMDA) receptor antagonists or opioid receptor agonists provide antinociception. Spinal coadministration of an NMDA receptor antagonist and morphine has an additive action for control of various pain states in animal models. The current study examined spinal coadministration of low doses of NMDA receptor antagonist, D-(-)-2-Amino-5-phosphonovalerate (D-APV), and mu-opioid receptor agonist, morphine sulfate (MS), in reducing visceral nociception using an acute bradykinin induced pancreatitis model in rats. METHODS: An intrathecal catheter was surgically inserted into the subarachnoid space for spinal drug administration in Sprague-Dawley rats. A laparotomy was performed for ligation and cannulation of the bile-pancreatic duct. Rats were pretreated intrathecally with artificial cerebrospinal fluid (aCSF), D-APV, MS, or combined administration of D-APV and MS. These treatments were given 30 min before noxious visceral stimulation with bradykinin injected through the bile-pancreatic catheter. Spontaneous behavioral activity tests, including cage crossing, rearing, and hind limb extension, were conducted before and after bradykinin injection into the bile-pancreatic duct to assess visceral nociception. RESULTS: Spinal pretreatment of D-APV or low doses of MS partially reduced visceral pain behaviors in this model. Pretreatments with combinations of low doses of MS (0.05-0.5 microg) and D-APV (1 microg) were maximally effective in returning all spontaneous behavioral activities to baseline. CONCLUSIONS: Spinal administration of combined doses of NMDA receptor antagonist, D-APV, and MS reversed three behavioral responses to induction of an acute pancreatitis model. These results suggest that in the clinical management of visceral pain, such as pancreatitis, restricted usage of glutamate antagonists might be useful as adjuvant potentiation at the onset of morphine therapy.     

Long-term treatment with darifenacin for overactive bladder: results of a 2-year, open-label extension study

OBJECTIVE: To examine, in a 2-year, non-comparative, open-label extension study, the safety, tolerability and efficacy of darifenacin controlled-release (CR) 7.5/15 mg once daily in patients with overactive bladder (OAB) who completed two 12-week randomized, double-blind, placebo-controlled 'feeder' studies. PATIENTS AND METHODS: Patients entering the extension received darifenacin 7.5 mg once daily for 2 weeks, after which a voluntary increase in dose to 15 mg was permitted. Thereafter, patients could adjust the dose (either 7.5 or 15 mg). Safety and tolerability were assessed from adverse events (AEs) and discontinuations. Efficacy was determined using various endpoints. RESULTS: In all, 716 patients entered the extension (mean age 57.3 years; 85.1% women) and 475 (66.3%) completed it (1089.9 patient-years of exposure). Darifenacin was well tolerated with no significant safety concerns. The most commonly reported AEs were dry mouth and constipation (all-causality rates 23.3% and 20.9%, respectively), leading to discontinuation in 1.3% and 2.4% of patients, respectively. Constipation infrequently required intervention, and analysis of bowel-habit questionnaires revealed that the reporting of constipation was related to minor changes in bowel habit rather than true constipation. The efficacy of darifenacin was maintained, including significant improvements in the number of incontinence episodes/week (median change -84.4% at 2 years, P < 0.001 vs feeder-study baseline). After 2 years, > 40% of patients achieved a > or = 90% reduction in incontinence episodes/week. CONCLUSION: In the first published 2-year, open-label study of a CR antimuscarinic agent, darifenacin 7.5/15 mg once daily had a favourable safety, tolerability and efficacy profile during the long-term treatment of OAB. As such, darifenacin represents a valuable therapeutic option for OAB.