The role of catecholamines in the pathogenesis of neurogenic pulmonary edema associated with subarachnoid hemorrhage

Background

Neurogenic pulmonary edema (NPE) occurs frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been suggested as its principal cause. The objective of this retrospective study is to evaluate the relative contribution of each catecholamine in the pathogenesis of NPE associated with SAH.

Methods

Records of 63 SAH patients (20 men/43 women) whose plasma catecholamine levels were measured within 48?h of SAH onset were reviewed, and the clinical characteristics and laboratory data of those who developed early-onset NPE were analyzed thoroughly.

Results

Seven patients (11?%) were diagnosed with NPE on admission. Demographic comparison revealed that the NPE+ group sustained more severe SAH than the NPE? group. Cardiac dysfunction was also significantly more profound in the former, and the great majority of the NPE+ group sustained concomitant cardiac wall motion abnormality. There was no significant difference in the plasma epinephrine levels between NPE+ and NPE? group (324.6?±?172.8 vs 163.1?±?257.2?pg/ml, p?=?0.11). By contrast, plasma norepinephrine levels were significantly higher in the NPE+ group (2977.6?±?2034.5 vs 847.9?±?535.6?pg/ml, p?<?0.001). Multivariate regression analysis revealed that increased norepinephrine levels were associated with NPE (OR, 1.003; 95?% CI, 1.002–1.007). Plasma epinephrine and norepinephrine levels were positively correlated (R?=?0.48, p?<?0.001). According to receiver operating characteristic curve analysis, the threshold value for plasma norepinephrine predictive of NPE was 2,000?pg/ml, with an area under the curve value of 0.85.

Conclusions

Elevated plasma norepinephrine may have more active role in the pathogenesis of SAH-induced NPE compared with epinephrine, although both catecholamines may be involved via multiple signaling pathways.     

Estimated low risk of rupture of small-sized unruptured intracranial aneurysms (UIAs) in relation to intracranial aneurysms in patients with subarachnoid haemorrhage

Objective

International guidelines for the management of unruptured intracranial aneurysms (UIAs) recommend observation in aneurysms <10 mm due to the estimated low risk of rupture. The aim of our study was analyse the data of recently treated patients with ruptured cerebral aneurysms with the special focus on size and configuration in view of the frequency scale in a daily routine setting.

Methods

We reviewed the data of all patients with aneurysmal subarachnoid haemorrhage (SAH) during the last 24 months at our institution. Configuration and size of the aneurysms were measured. Clinical data were collected using the following classifications for analysis: Hunt and Hess (H&H), modified Rankin Scale (mRS) and Fisher classification.

Results

Data of 135 patients with aneurysmal SAH (98 women, 37 men; ratio 2.6:1) were analysed. Analysis showed that 19 aneurysms (14 %) were >10 mm (mean size, 19.2 mm) and 116 aneurysms (85.9 %) <10 mm (mean size, 6.2 mm). In total, 112 were categorised as berry-like configured aneurysms (n?=?113 <10 mm, n?=?3 >10 mm), 18 as multi-lobar (n?=?16 <10 mm, n?=?2 >10 mm) and 5 as fusiform (n?=?4 <10 mm, n?=?1, >10 mm).

Conclusion

Since the results of our study showed that the majority of the aneurysms are <10 mm (mean, 6.2 mm), it is justified to challenge the recommendations of the international guidelines in a daily routine setting. We believe that the published data are not convincing enough to play a guidance role in daily routine. Due to improving surgical and endovascular techniques with satisfying results and the high number of ruptured small aneurysms, we believe a change in attitude in management of small-sized aneurysms is needed. Further diagnostic models are needed to determine the risk of rupture of intracranial aneurysms properly to obtain adequate treatment for UIAs.     

Intravenous paracetamol for fever control in acute brain injury patients: cerebral and hemodynamic effects

Background

Fever occurs frequently in acute brain injury patients, and its occurrence is associated with poorer outcomes. Paracetamol, an antipyretic frequently employed in patients with cerebral damage, may cause hypotension. We evaluated the cerebral and hemodynamic effects of intravenous (IV) paracetamol for the control of fever in Neuro-Intensive Care Unit (NICU) patients.

Methods

This is a prospective observational study in which we enrolled 32 NICU patients: Subarachnoid Hemorrhage (SAH, n?=?18), Traumatic Brain Injury (TBI, n?=?10), Intracerebral Hemorrhage (ICH, n?=?2) and Acute Ischemic Stroke (AIS, n?=?2).

Results

The administration of paracetamol resulted in a decrease of core body temperature (Tc) (p?=?0,0001), mean arterial pressure (MAP) (p?=?0,0006), cerebral perfusion pressure (CPP) (p?=?0,0033), and jugular venous oxygen saturation (SjVO2) (p?=?0.0193), and in an increase of arteriojugular venous differences of oxygen (AVDO2) (p?=?0.0012). The proportion of patients who had an infusion of norepinephrine increased from 47 % to 75 % (p?=?0.0039 McNemar Test). When intracranial pressure (ICP) at the start of paracetamol infusion (t-0) was compared with the measurement of ICP after 2 h, a significant correlation was observed (r?=?0.669, p?=?0.0002). This marked and significant correlation can be explained by the fact that for the higher levels of ICP assessed at t-0 (greater than 15 mmHg), we observed a marked reduction of ICP concomitant with the decrease of Tc. No problems related to norepinephrine administration and/or increase in dosage were observed.

Conclusion

Paracetamol administration is effective but exposes patients to hypotensive episodes that must be recognized and treated expeditiously to prevent further damage to the injured brain.     

Management of poor-grade patients with aneurysmal subarachnoid hemorrhage in the acute stage: Importance of close monitoring for neurological grade changes

BACKGROUND: The optimal management of poor-grade patients with aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We evaluated therapeutic outcomes to identify appropriate treatments for SAH patients admitted with a poor grade. METHODS: We retrospectively studied 136 patients admitted within 6 hours after SAH onset with a poor Hunt & Kosnik Grade (IV and V). RESULTS: Of 136 poor-grade patients, 20 with massive intracerebral or subdural hematoma underwent urgent hematoma evacuation and aneurysmal neck clipping. Seven of these achieved a favorable outcome (good recovery or moderate disability). Another 7 patients with prominent hydrocephalus or massive intraventricular hematoma underwent urgent continuous ventricular drainage. Of these, 4 manifested spontaneous grade improvement and underwent neck clipping; the other 3 died resulting from rebleeding. The remaining 109 patients whose poor grade was primarily because of SAH were observed without immediate surgery. In 43 patients of 109, the grade improved within 24 hours after hospitalization and within 38 hours in the other 4 patients. Aneurysmal neck clipping was performed in these 47 patients and a favorable outcome was achieved in 25 patients. The remaining 62 patients did not improve and the outcome was unfavorable. CONCLUSIONS: Poor-grade SAH patients should be treated according to the pathogenesis underlying their poor grade. Close monitoring for a grade change over the first 24 hours after hospitalization is mandatory in patients whose poor grade is primarily because of the SAH and helps to determine the appropriateness of surgery.     

The sympathetic response to profound hypothermia and circulatory arrest in infants

It has been suggested that the increased incidence of ventricular arrhythmias recognized below 30°C might be catecholamine mediated. Elevated catecholamine concentrations have been reported in experimentally induced hypothermia in animals. Plasma concentrations of epinephrine and norepinephrine were measured during profound hypothermia and total circulatory arrest in infants under one year of age undergoing surgical correction of congenital cardiac defects. There was no significant change in either epinephrine or norepinephrine levels during surface cooling to 28° C. Circulatory arrest and exsanguination at 18° C were not associated with a rise in catecholamine levels. However, there was a striking rise in the levels of both epinephrine and norepinephrine with the recommencement of bypass and rewarming. The mean plasma norepinephrine concentration rose from 466 pg/ml (SE ± 81) at circulatory arrest to 4543 pg/ml (SE ± 2058) on rewarming bypass (p < 0.02), while the mean plasma epinephrine concentration rose from 218 pg/ml (SE ± 54) at circulatory arrest to 3724 pg/ml (SE ± 1064) on rewarming bypass (p < 0.02). The plasma catecholamine concentrations fell once cardiopulmonary bypass was discontinued, when the infant’s temperature was 37° C. It would, therefore, appear unlikely that the ventricular irritability recognized below 30° C is due to catecholamine excess. The accumulation of catecholamines and/or metabolic products in the infants during circulatory arrest with their subsequent release into the circulation during rewarming may account for the elevation of catecholamine levels during rewarming bypass.     

Acute and Chronic Effects of Biliopancreatic Diversion with Duodenal Switch Surgery on Plasma Visfatin and Apelin Levels in Patients with Severe Obesity

Background

Visfatin is an adipokine linked to obesity and inflammation, and it has insulin-mimetic properties. Apelin is an adipokine with positive cardiac inotropic effects, and it may be related to inflammatory molecules. Variations in plasma visfatin and apelin levels following bariatric surgery remain controversial.

Methods

In this study, patients who underwent a biliopancreatic diversion with duodenal switch (BPD-DS) were compared to a severely obese group (control group). Anthropometric measures and blood samples were taken before surgery, on days 1 and 5, as well as at 6 and 12 months after surgery in the BDP-DS group. For the control group, the tests were performed at baseline and at 6 and 12 months.

Results

Seventy subjects in the BPD-DS group and 28 in the control group were included. The expected reduction in body weight at 1 year after a BPD-DS was observed (85.9?±?18.5 vs. 136.6?±?27.7 kg at baseline; p?<?0.001). Plasma visfatin levels decreased at day 1 (16.13?±?5.56 vs. 18.82?±?7.36 ng/mL at baseline; p?=?0.001), while plasma apelin levels decreased at day 5 (0.50?±?0.28 vs. 0.55?±?0.33 ng/mL at baseline; p?=?0.040) after surgery. There were no changes at 6 and 12 months compared to baseline, and no changes were observed in the control group.

Conclusions

Our data show that 1-year weight loss induced by BPD-DS did not influence the overall plasma visfatin and apelin levels in severely obese patients.     

The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

Plasma and cerebrospinal fluid (CSF) endothelin (ET)-1-like immunoactivity in 27 patients with aneurysmal subarachnoid hemorrhage (SAH) was measured serially by radioimmunoassay for 2 weeks after SAH onset. Mean ET-1-like immunoactivity levels in plasma of patients with SAH were highly elevated during the whole study period, while the levels in CSF of the same patients were not. Plasma ET-1-like immunoactivity levels in patients with SAH classified as Fisher computerized tomography (CT) Group 3 were higher than those in patients with SAH classified as Fisher CT Groups 1 and 2. There were no significant differences in plasma ET-1-like immunoactivity levels between the patient groups stratified by Hunt and Kosnik grade. In this series, plasma ET-1-like immunoactivity levels in the 12 patients with vasospasm were higher than those in the 15 patients without vasospasm during the 1st week; CSF ET-1-like immunoactivity levels in patients with vasospasm were in the normal range on Days 0 to 3 after SAH onset, then became elevated on Days 5 to 7 and remained high until the end of the 2nd week. In contrast, CSF ET-1-like immunoactivity levels in patients without vasospasm were within the normal range during the entire period of study. The time course of the occurrence of vasospasm and that of the increase in CSF ET-1-like immunoactivity coincided precisely. The possible role of endogenous ET-1 in the pathogenesis of vasospasm due to SAH is discussed.     

The rhPTH treatment elevates plasma secreted protein acidic and rich in cysteine levels in patients with osteoporosis

Summary

The secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, plays an important role in osteoblast formation, maturation, and survival. Here, we report the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment significantly increased plasma SPARC levels, and the change of plasma SPARC correlated positively with changes of lumbar bone mineral density (BMD) at L2–L4. These results unveil that SPARC may be a novel marker related to the regulation of bone formation.

Introduction

rhPTH (1-34) is known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines. SPARC is the most abundant noncollagenous extracellular matrix protein in the bone. So far, however, no study has reported the effects of rhPTH (1-34) administration on plasma SPARC levels in patients with osteoporosis. The purpose of this study was to compare the response of SPARC and BMD to rhPTH (1-34) and elcatonin in postmenopausal women with osteoporosis.

Methods

Women were randomized to either once-daily subcutaneous injection of rhPTH (1-34) (20 μg, N?=?89) or once-weekly intramuscular injection of elcatonin (200 U, N?=?35) for 12 months. Plasma biochemical markers of bone turnover and BMD were measured at baseline, 6 and 12 months after treatment.

Results

At baseline, plasma SPARC levels correlated positively with lumbar spine BMD in all patients (r?=?0.45, p?=?0.001). Compared with baseline, at 12 months, rhPTH (1-34) significantly increased lumbar spine BMD and plasma SPARC levels (p?=?0.008 and p?=?0.001, respectively), whereas elcatonin was ineffective. More importantly, the changes of plasma SPARC correlated positively with changes of lumbar BMD at L2–L4 (r?=?0.47, p?=?0.001) in the rhPTH (1-34)-treated group, but not in the elcatonin group.

Conclusion

The increase in plasma SPARC levels during the rhPTH (1-34) treatment may have contributed to the anabolic effect on bone formation, and SPARC may be a novel marker related to the regulation of bone formation.     

Effects of propiverine hydrochloride, an anticholinergic agent, on urethral continence mechanisms and plasma catecholamine concentration in rats

Introduction and hypothesis

Anticholinergics are used to treat overactive bladder. Anticholinergic agents such as propiverine hydrochloride reportedly increase plasma catecholamine levels in rats. It is also known that active urethral closure mechanisms prevents stress urinary incontinence (SUI), which is enhanced by central and peripheral noradrenergic system activation. Therefore, we examined the influence of propiverine hydrochloride on urethral anti-incontinence function in rats.

Methods

Adult female rats were divided into propiverine and vehicle-treated groups. The propiverine group was given propiverine orally once a day for 2 weeks, after which urethral function and plasma concentrations of catecholamine (dopamine, norepinephrine, epinephrine) were tested.

Results

Urethral baseline pressure measured by a microtransducer-tipped urethral catheter and leak-point pressure during passive intravesical pressure elevation were significantly increased in the propiverine group compared with the vehicle group. Plasma norepinephrine and epinephrine levels in the propiverine group were also significantly increased.

Conclusions

Propiverine treatment that increases plasma catecholamine levels could contribute to improvement of SUI conditions by increasing urethral resistance.     

BMD improvements after operation for primary hyperparathyroidism

Purpose

This study aims to quantify bone mineral density (BMD) changes following surgery in patients with primary hyperparathyroidism (PHPT) and to assess their relationship with clinical and biochemical variables.

Methods

A historic cohort of 236 PHPT patients with DXA scans pre- and 1-year postoperatively, clinical data, and biochemical data was analyzed.

Results

The mean age was 60 years (range 19–86) and 81 % of the patients were women. A significant postoperative 2.6 % (95 % CI, 2.1; 3.1) increase in lumbar spine BMD was seen. The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.002), Ca²⁺ (p?<?0.001), and alkaline phosphatase (p?=?0.014). Hip BMD increased 1.5 % (1.1; 1.9). The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.005) and Ca²⁺ (p?<?0.001) and inversely associated with plasma creatinine (p?=?0.004) and age (p?=?0.018). Total forearm BMD did not change significantly (?0.2 % (?0.5; 0.1)). An increase in forearm BMD was seen in 38 % of all patients, and the changes were positively associated with plasma PTH (p?<?0.001) and Ca²⁺ (p?=?0.009). In all 91 patients with mild PHPT (plasma Ca²⁺?<?1.45 mmol/l), there was a significant postoperative increase in spine BMD (1.9 % (1.2; 2.7)) and in hip BMD (1.0 % (0.4; 1.6)), but not in the forearm BMD (?0.3 % (?0.7; 0.2)). The postoperative BMD gain was higher in the hip and forearm in patients operated for adenomas compared with patients treated for hyperplasia.

Conclusions

We found significant postoperative BMD improvements both at the hip and the spine. BMD improvements were also significant in mild cases. At all scan sites, there were positive associations between preoperative plasma PTH levels and postoperative BMD increases. The measured BMD changes may mainly be due to a decrease in PTH-induced bone turnover with refilling of the remodeling space.     

The value of perfusion computed tomography in predicting clinically relevant vasospasm in patients with aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia remains a severe potential complication of aneurysmal subarachnoid hemorrhage (SAH) possibly leading to death and disability. We evaluated a semiquantitative and visual analysis of perfusion computed tomography (PCT) as a predictor of clinically relevant vasospasm (CRV) in patients with aneurysmal SAH. Thirty-eight patients with aneurysmal SAH were analyzed yielding 145 PCT scans. PCT, clinical examination, and transcranial Doppler ultrasound (TCD) were performed on days 3, 7, 10, and 14 after hemorrhage. Cerebral blood flow, cerebral blood volume, and time to peak (TTP) were analyzed semiquantitatively using six regions of interest, and visually for signs of cerebral hypoperfusion. CRV was defined as secondary cerebral infarction (CI) seen on cranial computed tomography scans and/or delayed neurological deterioration (DND). CI occurred in 13 (34.2 %) and DND in 11 patients (28.9 %). With TCD as pretest, TTP had a sensitivity of 90 % and a specificity of 72 % (cutoff value, 0.963) as predictor for CI. TTP’s sensitivity as predictor for DND was 90 % with a specificity of 61.1 % (cutoff value, 0.983). Visual analysis of TTP showed a negative predictive value of 100 % with a positive predictive value of 52 %. TTP is a sensitive and specific perfusion parameter in predicting CI in patients with SAH. Its use in the clinical setting may optimize the early treatment of patients at risk for vasospasm before the onset of clinical deterioration, especially when applying TCD as pretest. Further investigation in a larger patient population is required.     

Neuropsychological assessments in patients with aneurysmal subarachnoid hemorrhage, perimesencephalic SAH, and incidental aneurysms

Subarachnoid hemorrhage (SAH) is known to be associated with long-term cognitive deficits. Neurosurgical manipulation on the brain itself has been reported to have influence on neuropsychological sequelae. The following is a comparative study on perimesencephalic and aneurysmal subarachnoid hemorrhage patients as well as elective aneurysm patients that was carried out to determine the isolated and combined impact of surgical manipulation and hemorrhage, respectively, on long-term neuropsychological outcome. Inclusion criteria were good neurological recovery at discharge (modified Rankin Scale 0 or 1) without focal neurological deficit. Standardized psychological testing covered attention, memory, executive functions, and mood. Thirteen aneurysmal SAH patients, 15 patients undergoing elective clipping, and 14 patients with perimesencephalic SAH were analyzed. Standardized neuropsychological testing and social/professional history questionnaires were performed 2 years (mean) after discharge. Memory impairment and slower cognitive processing were found in the aneurysmal and perimesencephalic SAH groups, while elective aneurysm patients showed signs of impaired attention. However, compared with norm data for age-matched healthy controls, all groups showed no significant test results. In contrast, signs of clinical depression were seen in 9/42 patients, 45 % of all patients complained of stress disorders and 55 % of patients were unable to work in their previous professions. Nearly normal neuropsychological test results on long-term follow-up in SAH patients were unexpected. However, a 50 % rate of unemployment accompanied with stress disorders and depression manifests insufficient social and workplace reintegration. Therefore, even more specific rehabilitation programs are required following inpatient treatment to attain full recovery.     

Six Months of Treatment with the Endoscopic Duodenal-Jejunal Bypass Liner Does Not Lead to Decreased Systemic Inflammation in Obese Patients with Type 2 Diabetes

Obesity is associated with chronic low-grade systemic inflammation. Bariatric surgery has been shown to reduce this inflammation. Here, the effect of a nonsurgical bariatric technique, the duodenal-jejunal bypass liner (DJBL), on systemic inflammation was investigated. Seventeen obese patients with type 2 diabetes were treated with the DJBL for 6 months. Plasma C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were determined prior to and during DJBL treatment. Three months after initiation of DJBL treatment, TNF-α levels had increased from 1.8?±?0.1 to 2.1?±?0.1 pg/mL, whereas IL-6 increased from 2.7?±?0.3 to 4.0?±?0.5 pg/mL (both p?<?0.05). CRP and MPO also increased, though the differences were not significant. After 6 months, the levels of all parameters were similar to baseline levels (CRP, 4.2?±?0.6 mg/L; TNF-α, 2.0?±?0.1 pg/mL; IL-6, 3.5?±?0.5 pg/mL; MPO, 53.6?±?ng/mL; all p?=?ns compared to baseline). In the current study, 6 months of endoscopic DJBL treatment did not lead to decreased systemic inflammation.     

Urinary monocyte chemoattractant protein-1 correlates with disease activity in lupus nephritis

Monocyte chemoattractant protein-1 (MCP-1) has a pathogenic role in murine lupus nephritis (LN). We recruited 25 pediatric and adolescent systemic lupus erythematosus (SLE) patients from our lupus clinic [13 (52%) patients with LN and 12 (48%) lupus non-nephritis patients] and evaluated their urinary and plasma MCP-1 levels compared to adult and childhood controls. The median age and SLE disease duration of patients were 14.4 and 5.5 years, respectively. LN patients had a higher median renal (p?=?0.01) British Isles Lupus Assessment Group (BILAG) index, with a tendency for higher total BILAG scores (p?=?0.2). There were significantly increased urinary MCP-1 levels in the LN patients compared to healthy controls (p?<?0.001) whose values were significantly higher than lupus non-nephritis children (p<?0.004). Urinary MCP-1 levels correlated well with total BILAG scores (r?=?0.82, p?=?0.04). There were no differences in plasma MCP-1 levels between SLE patient groups and pediatric controls, although the levels in the childhood controls were elevated compared to those of the adult controls (p?<?0.04). These results provide evidence of increased urinary—but not plasma—MCP-1 levels in children with LN, which correlates well with SLE disease activity as measured by the BILAG index.     

The value of the Charlson Co-morbidity Index in aneurysmal subarachnoid haemorrhage

Background

Several studies have included different co-morbid conditions in prediction models for stroke patients. For subarachnoid haemorrhage (SAH), it is not known whether the Charlson Co-morbidity Index (CCI) is associated with outcome. We evaluated if this index was associated with outcome in patients with ruptured intracerebral aneurysms.

Methods

The data of all consecutive aneurysmal SAH (aSAH) patients treated at the Radboudumc, Nijmegen, The Netherlands and entered in the database were retrospectively analysed. Clinical condition at admission was recorded using the WFNS (World Federation of Neurological Surgeons Grading System) grade was collected, as were the age and treatment modality. The burden of co-morbidity was retrospectively registered using the CCI. Outcome was dichotomised on the modified Rankin Scale (mRS; 0–2, favourable outcome; 3–6, unfavourable outcome). A binary logistic regression analysis was performed.

Results

Between 6th May 2008 and 31st July 2013, 457 patients were admitted because of non-traumatic SAH (aSAH). Seventy-seven (16.8 %) patients had no aneurysm. Of the 380 patients with aSAH, information on co-morbid conditions was available for 371 patients. Thirty-six of those 371 had no treatment because of: bad clinical condition in 34 (9.2 %), a non-treatable dissecting aneurysm in 1 (0.3 %) and the explicit wishes of another. Co-morbidity was present in 113 (31.5 %) patients. Binary logistic regression analysis revealed no added value of using the CCI in predicting the outcome (p?=?0.91).

Conclusions

This study reports that the CCI is not associated with the outcome classified on the mRS at 6 months in patients after aSAH. The CCI has no added value in case-mix correction.     

Changes of endothelin concentration in cerebrospinal fluid and plasma of patients with aneurysmal subarachnoid hemorrhage

To investigate the clinical significance of endothelin (ET), a potent vasoconstrictor peptide, in subarachnoid hemorrhage (SAH) and SAH-related cerebral vasospasm, we measured the ET-like immunoreactivity (ETLI) in plasma and cerebrospinal fluid (CSF) obtained serially from patients with SAH due to ruptured cerebral aneurysm who underwent aneurysmal surgery. The normal ET–LI levels in plasma and CSF (n = 24) were 12.4±2.0 (mean±s.d.) and 9.1±1.2 pg·ml^-1, respectively. Plasma ET-LI levels in patients with SAH before surgery (16.8±7.8 pg·ml^-1, n = 8) were higher than the normal values ( P <0.05), and became further elevated after surgery (22.5±9.4 pg·ml^-1). ET-LI levels in plasma and CSF one day after surgery were 18.7±5.5 and 18.4±6.8 pg·ml^-1 ( P <0.01 vs. normal values), respectively, and declined thereafter. The plasma and CSF ET-LI levels in patients who showed symptomatic vasospasm became concomitantly elevated again. These results suggest that ET is involved in SAH-related vasospasm and raise the possibility that surgical stress influences the vasospasm.     

Effect of Bariatric Surgery on Bone Mineral Density: Comparison of Gastric Bypass and Sleeve Gastrectomy

The aim of our study was to compare bone mineral density (BMD) a year after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in age- and body mass index-matched women. In 33 morbidly obese women undergoing RYGB and 33 undergoing SG, plasma determinations of calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH) D₃), and insulin-like growth factor-I (IGF-I) were made prior to and at 12 months after surgery. Dual-energy X-ray absorptiometry was performed in all patients 1 year after surgery. BMD at the femoral neck and the lumbar spine 1 year after surgery was similar in women undergoing RYGB and SG (1.01?±?0.116 vs. 1.01?±?0.122 g/cm², p?=?0.993; 1.05?±?0.116 vs. 1.08?±?0.123 g/cm², p?=?0.384). The percentage of patients with osteopenia and osteoporosis was not different between groups. In the linear regression analysis, age (β?=??0.628, p?=?0.034) and lean mass 12 months after surgery (β?=?0.424, p?=?0.021) were found to be the main determinants of femoral neck BMD. Age (β?=??0.765, p?=?0.025), menopause (β?=??0.898, p?=?0.033), and lean mass (β?=?0.615, p?=?0.023) were determinants of BMD at the lumbar spine. No influence was found between low bone mass and type of surgery, plasma PTH, 25(OH) D₃, or IGF-I. The effect of RYGB and SG on BMD was comparable a year after surgery. Menopausal women were at a higher risk of having low bone mass, but the presence of osteoporosis was uncommon.     

Subarachnoid haemorrhage WFNS grade V: is maximal treatment worthwhile?

Background

Aneurysmal subarachnoid haemorrhage (SAH) WFNS grade V is commonly known to be associated with high mortality and a very poor prognosis for survivors. Therefore, maximal invasive therapy is frequently delayed until any spontaneous improvement with or without an external ventricular drainage occurs. The aim of the study was to verify possible predictive factors and the probability of a favourable outcome in maximally treated patients.

Methods

One hundred and thirty-eight consecutive patients with WFNS grade V SAH were admitted between 03/2006 and 12/2010. Thirty-five patients died before aggressive therapy could proceed. One hundred and three patients received maximal treatment and were retrospectively evaluated. The outcome was assessed at discharge and in the follow-up with the Glasgow Outcome Scale. Univariate and multivariate linear regression models were performed to find predictors for an unfavourable outcome.

Results

Despite treatment, early mortality was 30 % (n?=?31). At discharge, the rate of both vegetative and severely disabled patients was 27 % (n?=?28). Favourable outcome at discharge was observed in 16 % (n?=?16) of cases, whereas in the follow-up it rose to 26 % (n?=?27). Multivariate full model regression identified intraventricular haematoma (IVH) and increasing age as independently predictive for poor outcome.

Conclusions

Despite treatment, initial mortality and severe disability remain high. Nevertheless, a favourable outcome was achieved in 26 % of aggressively treated patients, rendering the withdrawal of maximal therapy for WFNS grade V SAH patients unacceptable today. In cases of old patients with IVH, the indication for aggressive therapy should be put in place more carefully due to a very poor prognosis.     

In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage

Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24 h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p = 0.02, OR = 3.16, 95%CI = [1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.