Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma

Objective

Severe traumatic brain injury (TBI) has a major role in mortality rate among the other types of trauma. The aim of this clinical study was to assess the effect of progesterone on the improvement of neurologic outcome in patients with acute severe TBI.

Methods

A total of 76 patients who had arrived within 8 h of injury with a Glasgow Coma Score ≤8 were enrolled in the study. In a randomized style 38 received progesterone (1 mg/kg per 12 h for 5 days) and 38 did not.

Results

There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period (50% vs. 21%); subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5–8 (p = 0.03).

Conclusion

The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury, especially those with 5 ≤ GCS ≤ 8, providing a potential benefit to the treatment of acute severe TBI patients. Considering this drug had no significant side effects, so progesterone could be used in patients with severe TBI as a neuro-protective drug.     

Spectroscopy-supported frame-based image-guided stereotactic biopsy of parenchymal brain lesions: Comparative evaluation of diagnostic yield and diagnostic accuracy

Objective

Comparative evaluation of diagnostic efficacy of stereotactic brain biopsy performed with and without additional use of spectroscopic imaging (¹H-MRS) for target selection was done.

Methods

From 2002 to 2006, 30 patients with parenchymal brain lesions underwent ¹H-MRS-supported frame-based stereotactic biopsy, whereas in 39 others MRI-guided technique was used. Comparison of diagnostic yield of the procedure in these two groups was performed. Additionally, the diagnostic accuracy was evaluated in 37 lesions, which were surgically resected within 1 month thereafter.

Results

Stereotactic biopsy permitted establishment of a definitive histopathological diagnosis in 57 cases and diagnosis of low-grade glioma without specific tumor typing in 8 cases. In 4 cases tissue sampling was non-diagnostic. In 5 out of 8 cases with incomplete diagnosis and in all non-diagnostic cases target selection was performed without the use of ¹H-MRS (P = 0.2073). The diagnostic yields of ¹H-MRS-supported and MRI-guided procedures were 100% and 90%, respectively (P = 0.1268). Comparison of the histopathological diagnoses after stereotactic biopsy and surgical resection revealed complete diagnostic agreement in 13 cases, minor disagreement in 14 cases, and major disagreement in 10 cases. Among these last 10 cases, initial undergrading of non-enhancing WHO grade III gliomas was the most common (7 cases). The diagnostic accuracy of ¹H-MRS-supported and MRI-guided procedures was 67% and 79%, respectively (P = 0.4756).

Conclusion

While in the present study the diagnostic yield of ¹H-MRS-supported frame-based stereotactic brain biopsy was 100%, its statistically significant diagnostic advantages over MRI-guided technique were not proved. Optimal selection of the spectroscopic target for tissue sampling remains unclear.     

Evaluation of the prevalence of severe hyperhomocysteinemia in adult patients with thrombosis who underwent screening for thrombophilia

Introduction

Treatment with B-vitamins and betaine reduces the high risk of thrombosis in patients with homocystinuria, a metabolic syndrome that is characterized by severe hyperhomocysteinemia (HHcy). In contrast, there is no clear demonstration that B-vitamins reduce the risk of thrombosis in patients with mild HHcy: for this reason, many question the clinical utility of measuring total Hcy (tHcy) in patients with thrombosis. However, thrombosis may be the first clinical manifestation of homocystinuria in patients reaching adulthood without signs and symptoms of the syndrome.

Aim

1) to measure the prevalence of severe, previously undiagnosed, HHcy among patients with thrombosis 2) to profile these patients on the basis of their characteristics.

Methods

Six Italian Thrombosis Centers completed a first questionnaire, reporting tHcy levels in patients with thrombosis who underwent thrombophilia screening, and a second questionnaire, reporting the characteristics of patients with severe HHcy (tHcy > 100 μmol/L).

Results

Of 19,678 cross-sectionally collected patients with thrombosis who underwent thrombophilia screening in the last 12.5 years (median value, range 6-17), 38 had severe HHcy (0.2%). Their median age at diagnosis was 47 years (range 19-83) and the median level of tHcy was 130 μmol/L (range 101-262). Venous thromboembolism (71%) was more frequent than arterial thromboembolism (26%); recurrent thrombosis occurred in 42% of cases.

Conclusions

Measurement of tHcy in adult patients with thrombosis may reveal the presence of severe HHcy. Since treatment of patients with severe HHcy decreases the risk of thrombosis, measurement of tHcy in patients with thrombosis may prove clinically useful.     

Effects of subthalamic nucleus deep brain stimulation on sweating function in Parkinson's disease

Purpose

To assess the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on the sweating function in patients with advanced Parkinson's disease (PD).

Methods

Nineteen patients with idiopathic PD (mean age ± SD, 61.58 ± 9.47) were examined immediately before and 6 months after DBS. Each examination session included registration of autonomic symptoms by means of a semi-structural questionnaire and recording of sympathetic skin response (SSR) from both palms and one sole. The neurophysiological measurements were compared to those of 19 matched for sex and age healthy controls.

Results

Six months post-DBS motor improvement was amounted to 65.9% and the daily levodopa equivalent dose was decreased by 36.4%. Post-operatively, dyshidrosis manifestations were reduced by 66.7% (pre-DBS sudomotor dysfunction in 47.4% of patients and sudomotor fluctuation in 57.1% of the above patients). There were no significant differences in-between pre- and post-DBS results of SSR study. However, the number of patients with at least one abnormal SSR pre-operative was reduced from 6 to 3 post-operative. No correlation was found between this neurophysiological finding and the change of clinical symptoms of hyperhidrosis or the DBS motor improvement.

Conclusions

These results, although based on a small sample, suggest that STN DBS, in addition to the effect to the mobility, might also favorably regulate sweat in idiopathic PD.     

Cognitive dysfunctions and cerebral microbleeds in adult patients with haemophilia A: A clinical and MRI pilot-study

Background

Studies providing information about the cognitive profile of adult haemophiliacs are lacking.

Aims

To assess the neuropsychological profile in a group of Haemophiliac patients; to detect asymptomatic cerebral microbleeds (CMBs) and any correlation between CMBs and cognitive dysfunctions; to verify how several contributing factors may determine cognitive dysfunctions and/or Magnetic Resonance Imaging (MRI) findings.

Methods

Adult haemophiliacs without history of brain bleeding were prospectively enrolled on Padua Haemophilia Centre. Patients underwent: i) “Short Neuropsychological Test” assessing cognitive functions (Short Neuropsychological Examination) to obtain an overall cognitive performance (OCP) profile standardised on a cohort matched for age, sex, cultural profile; ii) MRI of the brain to evaluate areas of brain atrophy or haemorrhagic lesions. We collected information on anti-haemorrhagic treatment, cardiovascular risk profile, viral infections, birth trauma.

Results

49 adults with haemophilia (31 severe-moderate, 18 mild) were enrolled. 73% of patients presented a reduction in OCP. According to OCP, no significant difference between severe and mild haemophilia was observed though scores tended to be worse in severe haemophilia (mean Z score 0.20 ± 0.10 vs s0.15 ± 0.11). Considering risk factors, OCP correlated significantly with coronary artery disease (p = 0.02). MRI findings in 44 patients, indicated CMBs were inversely related to OCP (R = − 0.32 p < 0.05). CMBs were associated with cardiovascular risk factors (p = 0.018).

Conclusions

Adult haemophiliacs seem to present high prevalence of mild cognitive dysfunctions that doesn’t correlate with the severity of haemophilia probably for the few number of patients evaluated. OCP impairment seems to be related to the presence of CMBs and of risk factors for cardiovascular disease.     

Intraindividual comparison of histopathological diagnosis obtained by stereotactic serial biopsy to open surgical resection specimen in patients with intracranial tumours

Background

There are concerns in the literature about the accuracy of histopathological diagnosis obtained by stereotactic biopsy in patients with brain tumours. The aim of this study was to analyse intraindividually the histopathological accuracy of stereotactic biopsies of intracerebral lesions in comparison to open surgical resection.

Materials and methods

Between 2007 and 2011 a total of 635 patients underwent stereotactic serial biopsy in our department. Among these patients we identified 51 patients, who underwent magnetic resonance (MR) based stereotactic biopsy and subsequent open resection within 30 days. Mortality and morbidity data as well as final histopathological diagnoses of both procedures were compared with regard to tumour grade and tumour cell type. Patients with discrepancies between the histological diagnosis obtained by biopsy and open resection were classified into three subgroups (same cell type but different grading; same grading but different cell type and different grading as well as different cell type).

Results

The mean number of tissue samples taken by stereotactic serial biopsy from each patient was 12 (range 7–21). Minor morbidity was 6% and major morbidity was 14% after open surgery compared to no morbidity after stereotactic biopsy. Mortality was 2% after stereotactic biopsy (one patient died after stereotactic biopsy as a result of a fatal bleeding) compared to 0% in the resection group. Silent bleeding rate without any clinical symptoms was 8% in the biopsy group. A complete correlation of histopathological findings between the biopsy group and the resection group was achieved in 76% and was increased to 90% by analyzing clinical and neuroradiological information. In patients with recurrence the correlation was higher (94%) than for patients with primary brain lesions (67%). The discrepancies between the open resection group and biopsy group were analysed.

Conclusion

Stereotactic MR guided serial biopsy is a minimal invasive procedure with low morbidity and high diagnostic accuracy for diagnosis and grading of brain tumours. Diagnostic accuracy of stereotactic biopsy can be enhanced further by careful interpretation of neuroradiological and clinical information.     

Increased intracranial pressure is associated with the development of acute lung injury following severe traumatic brain injury

Objective

This study investigated the relationship among intracranial pressure (ICP), the development of acute lung injury (ALI) and systemic inflammatory response syndrome (SIRS) following a severe traumatic brain injury (TBI).

Methods

Post-traumatic ICP was continuously monitored for the first week following injury in a series of consecutive patients with isolated severe TBI. The initial ICP and the duration of intracranial hypertension (ICH) were calculated. The risk factors associated with the development of ALI and SIRS were evaluated.

Results

Of the 86 patients enrolled, 22 patients developed ALI and 52 patients developed SIRS during the observation period. The patients with ALI presented with a significantly higher initial ICP (31.3 ± 7.8 mmHg vs. 23.0 ± 8.8 mmHg, p < 0.001) and a longer duration of ICH (16.8 ± 6.5 h vs. 11.9 ± 6.0 h, p = 0.002) than those without ALI. The incidence of both ALI and SIRS increased with increasing initial ICP, and the presence of SIRS was associated with a fourfold increase in the risk of developing ALI (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.2–13.0).

Conclusions

Increased ICP is associated with increased risks of developing ALI and SIRS following severe TBI. Future studies designed to verify the causative relationship between increased ICP and the systemic responses are warranted.     

Hypercholesterolemia is associated with a lower risk of cerebral ischemic small vessel disease detected on brain checkups

Objective

Several studies have reported an association between low cholesterol levels and cerebral small vessel disease (SVD). In this study, we examined whether serum total cholesterol was associated with SVD, including lacunar infarctions and white matter hyperintensity, detected by magnetic resonance imaging (MRI), in participants who had a checkup of the brain.

Methods

We retrospectively investigated 6143 participants aged 40 and over who visited a hospital for a brain checkup in a cross-sectional design. We performed logistic regression analysis to examine the association between total cholesterol and SVD.

Results

SVD was observed in 1456 participants (24%). Adjusting for sex, age, body mass index, hypertension, hypertriglyceridemia, and diabetes, a total cholesterol ≥ 225 mg/dL (the highest quartile) was significantly associated with not having SVD compared with a total cholesterol < 178 mg/dL (the lowest quartile; odds ratio [OR], 0.708; 95% confidence interval [CI], 0.581–0.863). Participants with a total cholesterol of 200–225 mg/dL (the third quartile) tended to have a reduced risk of SVD (OR, 0.832; 95%CI, 0.689–1.005).

Conclusion

Hypercholesterolemia was significantly associated with a lower risk of SVD, detected by MRI, in participants undergoing a brain checkup, after adjusting for potential confounding factors, such as age and hypertension.     

Anti-cholinergics for axial symptoms in Parkinson's disease after subthalamic stimulation

Objective

We studied the effect of anti-cholinergic therapy on axial symptoms that show a tendency to worsen over time after deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD).

Patients and methods

We conducted a prospective study of 20 consecutive patients treated with the anti-cholinergic agent trihexyphenidyl after bilateral STN-DBS and assessed the effect of anti-cholinergic therapy on parkinsonism 1 month after its initiation using the Unified Parkinson's Disease Rating Scale (UPDRS).

Results

After a mean post-operative follow-up period of 22.3 months, the scores of axial symptoms on UPDRS part II (ADL score) and part III (motor score) deteriorated by 87% and 54% (baseline), respectively, compared with the pre-operative scores (P < 0.001 for both comparisons). After adding trihexyphenidyl to dopaminergic medication with stimulation, the scores of axial symptoms on UPDRS part II and part III improved from baseline by 33% and 39%, respectively (P < 0.001 for both comparisons).

Conclusions

Our findings demonstrated that the anti-cholinergic agent trihexyphenidyl shows positive effect for a patient population developing deterioration of axial symptoms after STN-DBS. The results in the present study may provide insights into the mechanism of emergence or progression of axial symptoms in patients with PD after STN-DBS.     

The number of involved extracranial organs: A new predictor of survival in breast cancer patients with brain metastasis

Objective

This study was performed to investigate the potential impact of the number of involved extracranial organs on survival in patients with brain metastasis from breast cancer.

Methods

The data of 196 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastases from breast cancer were retrospectively analyzed. Six potential prognostic factors were evaluated for associations with survival. These factors included WBRT regimen, age, Karnofsky performance score (KPS), number of brain metastases, interval from breast cancer diagnosis to WBRT, and the number of involved extracranial organs.

Results

The 6-month survival rates of patients with involvement of 0, 1, 2, 3 and ≥4 extracranial organs were 59%, 49%, 26%, 26% and 13%, respectively, and the 12-month survival rates were 45%, 36%, 17%, 17% and 13%, respectively (p < 0.001). On multivariate analysis, the number of involved extracranial organs (risk ratio 1.17; 95%-confidence interval 1.02–1.35; p = 0.028) maintained significance, as did KPS (p < 0.001), but not age (p = 0.27).

Conclusion

The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from breast cancer.     

Non confirmatory electroencephalography in patients meeting clinical criteria for brain death: Scenario and impact on organ donation

Objective

To describe the causes and outcome of adult patients with preserved electroencephalographic activity despite clinical findings suggesting brain death (BD), and its impact on organ donation.

Methods

Retrospective study of the clinical and electroencephalography (EEG) data of all adult patients admitted to our hospital between January 2001 and December 2011 in whom a comprehensive clinical diagnosis of BD was reached following absence of brainstem reflexes and confirmatory apnea tests, were obtained. All patients with clinical findings suggesting BD and an EEG showing brain activity were selected for the analysis. We calculated the brain death interval (BDI) as the time between the first complete clinical examination and confirmatory ancillary test, or the time between the first and second complete clinical examination for BD, in order to analyze the impact on family consent for organ donation.

Results

A complete clinical examination and EEG were diagnostic in 289 patients. In 279 (96.5%), the first EEG showed electrocerebral inactivity corroborating the clinical findings of BD. The mean BDI in this group was 4.2 ± 5.8 h (median; 1.8[1.0–3.5]). This value was significantly lower than in the group in which only two full clinical evaluations were performed (p < 0.0001). In 10 out 289 (3.5%), the first EEG showed at least some brain activity. The mean BDI in this group was 27.2 ± 13.8 h (median; 22.9 [19.1−31.2]). In two cases, a third EEG was necessary before obtaining electrocerebral inactivity. A BDI > 6 h, was positively associated with a family refusal for organ donation (p = 0.02).

Conclusions

The rate of EEGs with electrocerebral activity despite clinical findings suggesting BD was only 3.5%. It occurred most frequently with severe brainstem damage. Although in this small percentage of patients, BD diagnosis was notably delayed, in the great majority of cases the use of EEG shortened the BDI. In our series, a BD diagnosis delay >6 h negatively affected consent for organ donation.

Significance

The use of EEG can decrease the time interval for brain death diagnosis.     

Muscle biopsy findings predictive of malignancy in rare infiltrative dermatomyositis

Objective

The characteristic pathological muscular findings of polymyositis (PM) and dermatomyositis (DM) have been shown to reflect their different pathogeneses. Here, we characterized the muscle biopsy findings of PM and DM patients with or without malignancy.

Methods

We evaluated the muscle biopsy findings of 215 consecutive PM and DM patients admitted to our hospital between 1970 and 2009. Pathology of the lesion biopsy sections was classified into 3 types: endomysial infiltration-type, perivascular infiltration-type, and rare-infiltrative-type.

Results

There was no difference between the muscle pathology of PM patients with and without malignancy. However, the incidence of rare-infiltrative type muscle pathology in DM patients with malignancy was significantly higher than in those without such tumors (p = 0.0345).

Conclusion

The incidence of rare-infiltrative type muscle pathology may be a predictive marker of DM with malignancy.     

Patent foramen ovale increases the risk of acute ischemic stroke in patients with acute pulmonary embolism leading to right ventricular dysfunction

Background

Patent foramen ovale (PFO) is an established risk factor for ischemic stroke. Since acute right ventricular dysfunction (RVD) observed in patients with PE can lead to right-to-left inter-atrial shunt via PFO, we hypothesized that PFO is a risk factor for ischemic stroke in PE with significant right ventricular dysfunction.

Methods

55 patients (31 F, 24 M), median age 49 years (range 19–83 years) with confirmed PE underwent echocardiography for RVD and PFO assessment. High risk acute PE was diagnosed in 3 (5.5%) patients, while 16 (29%) hemodynamically stable with RVD patients formed a group with intermediate-risk PE. PFO was diagnosed in 19 patients (34.5%). Diffusion-weighted MRI of the brain for acute ischemic stroke (AIS) was performed in all patients 4.91 ± 4.1 days after admission.

Results

AIS was detected by MRI in 4 patients (7.3%). Only one stroke was clinically overt and resulted in hemiplegia. All 4 AIS occurred in the PFO positive group (4 of 19 patients), and none in subjects without PFO (21.0% vs 0%, p = 0.02). Moreover, all AIS occurred in patients with RVD and PFO, and none in patients with PFO without RVD (50% vs 0%, p = 0.038).

Conclusion

Our data suggest that acute pulmonary embolism resulting in right ventricular dysfunction may lead to acute ischemic stroke in patients with patent foramen ovale. However, the clinical significance of such lesions remains to be determined.     

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS

Background

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics.

Objective

This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS).

Methods

99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10 Hz) left-side stimulation in 33 patients, and low frequency (1 Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p < 0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation.

Results

Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p = 0.017) or right stimulation (p < 0.001), without significant perfusion differences between these two subgroups.

Conclusions

These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group.     

Frontal lobe atrophy is associated with small vessel disease in ischemic stroke patients

Background

The pathogenesis of frontal lobe atrophy (FLA) in stroke patients is unclear. We aimed to ascertain whether subcortical ischemic changes were more associated with FLA than with parietal lobe atrophy (PLA) and temporal lobe atrophy (TLA).

Methods

Brain magnetic resonance images (MRIs) from 471 Chinese ischemic stroke patients were analyzed. Lobar atrophy was defined by a widely used visual rating scale. All patients were divided into non-severe, mild–moderate, and severe atrophy of the frontal, parietal, and temporal lobe groups. The severity of white matter lesions (WMLs) was rated with the Fazekas’ scale. Clinical and radiological features were compared among the groups. Subsequent logistic regressions were performed to determine the risk factors of atrophy and severe atrophy of the frontal, parietal and temporal lobes.

Results

The frequency of FLA in our cohort was 36.9% (174/471). Severe FLA occurred in 30 (6.4%) patients. Age, previous stroke, and periventricular hyperintensities (PVH) (odds ratio (OR) = 1.640, p = 0.039) were independent risk factors of FLA. Age and deep white matter hyperintensities (DWMH) (OR = 3.634, p = 0.002) were independent risk factors of severe FLA. PVH and DWMH were not independent risk factors of PLA and TLA.

Conclusion

Frontal lobe atrophy in ischemic stroke patients may be associated with small vessel disease. The association between WMLs and FLA was predominant over atrophy of the parietal and temporal lobes, which suggests that the frontal lobe may be vulnerable to subcortical ischemic changes.     

Prevalence of silent myocardial ischemia in single and multiple lacunar infarcts and large vessel disease stroke

Background and purpose

The relationships between single (SLI) and multiple lacunar infarcts (MLI) and occult coronary artery disease (CAD) have not yet been sufficiently evaluated. We aimed to investigate the prevalence of silent CAD in patients with SLI, MLI and large vessel disease (LVD) stroke, and to identify factors associated with its presence.

Methods

We enrolled 125 patients who had suffered their first non-cardioembolic ischemic stroke but had no documented history of CAD. According to their pathologies, these patients were assigned to one of three groups: MLI (n = 21), SLI (n = 50) or LVD (n = 54). Asymptomatic CAD was detected by myocardial perfusion SPECT imaging.

Results

Silent CAD was detected in 40 patients (32% of the total); of those that experienced CAD, 15 (30%) were from the SLI group, 7 (33%) had MLI, and 18 (33%) had an LVD stroke. Differences between the groups were not significant. During a median follow-up of 48 months, the overall stroke recurrence was 8.8%; the stroke recurrence rates for each subgroup were 6% in patients with SLI, 7% in LVD and 19% in MLI. Mortality was higher in patients from the MLI and LVD groups (26% and 14%, respectively) than in those from the SLI group (6%; p = 0.02). We found no relationships between the various risk factors and silent CAD.

Conclusions

In this exploratory study, SPECT imaging results revealed that the prevalence of abnormal myocardial perfusion was similar in patients with either single or multiple lacunar infarcts and those that had experienced large vessel disease stroke.     

Chronic kidney disease in patients with cancer and its association with occurrence of venous thromboembolism and mortality

Introduction

The risk for occurrence of venous thromboembolism (VTE) in cancer patients has been the aim of numerous investigations. Chronic kidney disease (CKD) is a frequent comorbidity in cancer patients and has been found to be a risk factor for VTE in the general population. We investigated the association of CKD with VTE and mortality in cancer patients.

Methods

Patients were recruited into the prospective cohort study, Vienna Cancer and Thrombosis Study (CATS). CKD was estimated with equations for glomerular filtration rate (eGFR) based on serum creatinine by Modification of Diet in Renal Disease (MDRD), CKD Epidemiology collaboration (CKD-EPI) and Cockcroft-Gault equation (C-G). Patients were subsequently classified to stages of CKD according to the Kidney Diseases Outcomes Quality Initiative. Primary endpoint was occurrence of VTE and secondary endpoint was death.

Results

The cohort of 1100 patients was prospectively followed over a median of 723 days. CKD with an eGFR of under 90 ml/min was common with a prevalence of 71.1%, 67.0% or 51.5% of patients calculated with MDRD, CKD-EPI and C-G equations, respectively, but severe CKD (eGFR < 30 ml/min) was rare. Patients with a moderately decreased eGFR (90-60 ml/min/1.73 m²) based on CKD-EPI had a subdistribution hazard ratio of 0.68 (95% confidence interval 0.43-1.06). An association between CKD and occurrence of VTE or mortality could also not be shown with the other equations.

Conclusions

In our investigation of a large cohort of cancer patients with a high prevalence of CKD, a reduced eGFR was not an independent risk factor for occurrence of VTE or death.     

The first survival score for patients with brain metastases from small cell lung cancer (SCLC)

Objective

Survival scores can help physicians select appropriate treatment for patients with brain metastasis. Primary tumors have different biological behavior justifying separate scoring systems for different tumors. In this study, a survival score was developed for patients with brain metastasis from SCLC.

Methods

Data of 172 patients receiving whole-brain radiotherapy alone for brain metastasis from SCLC were included. Patients were assigned to a test (N = 86) or a validation group (N = 86). In the test group, Karnofsky Performance Score, number of brain metastases, and extracranial metastasis were associated with survival and included in the score. Scores for each factor were obtained from the 6-month survival rate divided by 10. According to the total scores, which represented the sum of the three scores, three prognostic groups were formed.

Results

6-Month survival rates in the test group were 3% for 5–8 points, 40% for 9–12 points, and 89% for 15 points (p < 0.001). In the validation group, 6-month survival rates were 3%, 41%, and 89% (p < 0.001). The comparisons between the three prognostic groups of the test group and the validation group did not show significant differences.

Conclusions

This new score appears valid and reproducible. It can be used to personalize the treatment to patients with brain metastasis from SCLC.     

Serum soluble CD40 Ligand levels are associated with severity and mortality of brain trauma injury patients

Background

Serum soluble CD40 Ligand (sCD40L) levels, which exhibit prothrombotic and proinflammatory properties, have not been studied in patients with traumatic brain injury (TBI). Thus, the objective of this study was to determine whether serum sCD40L levels are associated with severity and mortality in patients with severe TBI.

Methods

This was a prospective, observational and multicenter study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of sCD40L were measured on the day of TBI. Endpoint was established in 30-day mortality.

Results

We found higher serum sCD40L levels (P < 0.001) in non-surviving TBI patients (N = 27) than in survivor ones (N = 73). Logistic regression analysis showed that serum sCD40L levels were associated with 30-day mortality (OR = 1.58; 95% CI = 1.12-2.21; P = 0.008) controlling for APACHE-II score and computer tomography findings. The area under the curve (AUC) for serum sCD40L levels as predictor of 30-day mortality was 0.79 (95% CI = 0.70-0.86; P < 0.001). Survival analysis showed that patients with serum sCD40L levels higher than 2.11 ng/mL presented increased 30-day mortality than patients with lower levels (Hazard ratio = 9.0; 95% CI = 4.25-19.27; P < 0.001). We found an association between serum sCD40L levels and APACHE-II (rho = 0.33; P = 0.001), and GCS score (rho = -0.21; P = 0.04).

Conclusions

To our knowledge, this is the first study reporting data on serum sCD40L levels in patients with severe TBI. The most relevant and newer findings of our study are that serum sCD40L levels in non-surviving patients with severe TBI are higher than in surviving ones, and that there are an association between serum sCD40L levels and TBI severity and mortality.     

Diagnostic impact of baseline cerebral blood flow in patients with acute ischemic stroke prior to intravenous recombinant tissue plasminogen activator therapy

Objective

To determine whether severe cerebral perfusion defects measured by SPECT prior to rt-PA therapy attribute to severe intracerebral hemorrhage (SICH).

Methods

We measured baseline cerebral blood flow (CBF) using technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT qualitatively prior to rt-PA therapy, in 52 consecutive patients (range 38–93 years). The degree and extent of the asymmetry of local CBF were analyzed semi-quantitatively. We did not administrate rt-PA in patients with severe perfusion defects. Clinical outcome and the incidence of SICH were studied.

Results

Three (5.8%) patients had severe perfusion defects that were undetected by CT and/or DWI. The other 49 (94.2%) patients had mild perfusion defects. The asymmetry of local CBF was 0.08 ± 0.08 (n = 3) and 0.3 ± 0.15 (n = 49) in the two groups, respectively. The percentages of the ipsilateral hemisphere in which perfusion was impaired severely were 17.5 ± 9.5% (n = 3) and 0.43 ± 0.87% (n = 49). Two patients were found petechial hemorrhage, but there was no patient who developed SICH in the former group following conventional antithrombotic therapy. In the latter group, SICH occurred in 1/49 (2.0%) patient following rt-PA therapy.

Conclusion

These results suggest that rt-PA therapy for patients with severe cerebral perfusion defects may cause SICH and baseline CBF may contribute to identify patients at high risk for SICH after intravenous rt-PA therapy.