The impact of repeated surgery and adjuvant therapy on survival for patients with recurrent glioblastoma

Objective

Treatment of glioblastoma recurrence can have a palliative aim, after considering risks and potential benefits. The aim of this study is to verify the impact of surgery and of palliative adjuvant treatments on survival after recurrence.

Methods

From January 2002 to June 2008, we treated 76 consecutive patients with recurrent glioblastoma. Treatment was: 1-surgery alone – 17 patients; 2-adjuvant-therapy alone – 24 patients; 3-surgery and adjuvant therapy – 16 patients; no treatment – 19 patients. The impact on median overall-survival (OS-time between recurrence and death/last follow-up) of age, Karnofsky performance scale (KPS), resection extent and adjuvant treatment scheme (Temozolomide alone vs low-dose fractionated radiotherapy vs others) was determined. Survival curves were obtained through the Kaplan–Meier method. Cox proportional-hazards was used for multivariate analyses. Significance was set at p < 0.05.

Results

Median OS was 7 months. At univariate analysis, patients with a KPS ≥ 70 had a longer OS (9 months vs 5 months – p < 0.0001). OS was 6 months for patients treated with surgery alone, 5 months for patients that received no treatment, 8 months for patients treated with chemotherapy alone, 14 months for patients treated with surgery and adjuvant therapy-p = 0.01. Patients with a KPS < 70 were significantly at risk for death – HR 2.8 – p = 0.001.Subgroup analysis showed no significant differences between patients receiving gross total or partial tumor resection and among patients receiving different adjuvant therapy schemes. Major surgical morbidity at tumor recurrence occurred in 16 out of 33 patients (48%).

Conclusion

It is fundamental, before deciding to operate patients for recurrence, to carefully consider the impact of surgical morbidity on outcome.     

A comparison between cyberknife and neurosurgery in solitary brain metastases from non-small cell lung cancer

Purpose

To evaluate the efficacy of cyberknife (CK) and neurosurgery (NS) in patients newly diagnosed as solitary brain metastasis (SBM) from non-small cell lung cancer (NSCLC).

Methods and materials

We retrospectively analyzed 76 patients between 1990 and 2012 from our institution, including 38 patients performing CK and the other half performing NS. The observation end point was overall survival time (OS), local control of treated metastasis (LC) and intracranial control (IC). Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS, LC and IC.

Results

The baseline characteristic between the two groups was not significantly different. The 1-year OS rates were 53.5% and 30.5% in the CK group and NS group, respectively, (p = 0.121). The 1-year LC rates were 50.8% and 31.3%, respectively, (p = 0.078). The 1-year IC rates were 50.8% and 27.7%, respectively, (p = 0.066). In multivariate analysis, improved OS was significantly associated with younger age (p = 0.016), better ECOG performance status (p = 0.000) and graded prognostic assessment (GPA, 3.5–4.0, p = 0.006). The LC was also associated with better ECOG performance status (p = 0.000). The IC was associated with both better ECOG performance status (p = 0.000) and GPA (3.5–4.0, p = 0.005).

Conclusions

There was no statistical difference between CK and NS for SBM from NSCLC in OS, LC and IC. However, CK is less invasive and may be more acceptable for patients. The result needs randomized trials to confirm and further study.     

Emotion suppression and mortality risk over a 12-year follow-up

Objective

Suppression of emotion has long been suspected to have a role in health, but empirical work has yielded mixed findings. We examined the association between emotion suppression and all-cause, cardiovascular, and cancer mortality over 12 years of follow-up in a nationally representative US sample.

Methods

We used the 2008 General Social Survey–National Death Index (GSS–NDI) cohort, which included an emotion suppression scale administered to 729 people in 1996. Prospective mortality follow up between 1996 and 2008 of 111 deaths (37 by cardiovascular disease, 34 by cancer) was evaluated using Cox proportional hazards models adjusted for age, gender, education, and minority race/ethnicity.

Results

The 75th vs. 25th percentile on the emotional suppression score was associated with hazard ratio (HR) of 1.35 (95% Confidence Interval [95% CI] = 1.00, 1.82; P = .049) for all-cause mortality. For cancer and cardiovascular disease mortality, the HRs were 1.70 (95% CI = 1.01, 2.88, P = .049) and 1.47 (95% CI = .87, 2.47, P = .148) respectively.

Conclusions

Emotion suppression may convey risk for earlier death, including death from cancer. Further work is needed to better understand the biopsychosocial mechanisms for this risk, as well as the nature of associations between suppression and different forms of mortality.     

Microvascular retinal abnormalities in acute intracerebral haemorrhage and lacunar infarction

Background

Retinal microvascular changes have been previously associated with cerebral MRI markers of small vessel disease (SVD). Whether retinal changes differ between patient with intracerebral haemorrhage (ICH) and patients with lacunar infarction (LI) caused by small vessel disease has been poorly investigated.

Objective

The study aims to compare the frequency of retinal changes between patients with LI and patients with ICH at the acute stage of stroke-related SVD.

Methods

Microvascular wall signs (arteriolar occlusion, arteriovenous nicking, focal arterial narrowing) and retinopathy lesions (microanevrysms, cotton wool spots, retinal haemorrhages, hard exudates) were assessed by retinography up to three months after stroke onset.

Results

Forty-eight non-diabetic patients with acute stroke-related to SVD (26 LI, 22 ICH) were recruited prospectively in the study. Retinal wall signs (arteriovenous nicking, and focal arterial narrowing) were found in more than three quarters of subjects and most often bilaterally in both groups. Retinopathy lesions (cotton wool spots, retinal haemorrhages) were found more frequently in ICH patients than in LI patients (22.2% vs. 15.4%, 50% vs. 34% respectively, P > 0.005). The frequency of bilateral cotton wool spots and of bilateral retinal haemorrhages was significantly higher in ICH patients than in LI patients (12.5% vs. 0%, P = 0.012, 41.2% vs. 7.7%, P = 0.029 respectively).

Conclusion

These results confirm the high frequency of microvascular alterations in patients with hypertension-related SVD leading to LI or ICH and suggest that retinal tissue alterations are more frequent in ICH than in LI. Further investigations are needed to investigate the mechanisms underlying this difference.     

Estimation of sleep disturbances using wrist actigraphy in patients with postural tachycardia syndrome

Study objectives

Patients with postural tachycardia syndrome (POTS) commonly complain of fatigue, unrefreshing sleep, daytime sleepiness and diminished quality of life. The study objective was to assess sleep quality in POTS patients using wrist actigraphy.

Design

Prospective study with control group.

Methods

Patients with POTS (n = 36) and healthy subjects (n = 36) completed a detailed sleep log and actigraphy for 7 days.

Results

Compared with healthy subjects, POTS patients have more self-reported problems including days with restless sleep (53 ± 30% vs. 21 ± 20%; P < 0.001) and tiredness (75 ± 23% vs. 39 ± 27%; P < 0.001). Using actigraphy, POTS patients have lower sleep efficiency (73 ± 13% vs. 79 ± 6%; P = 0.01). Actigraphy determined sleep onset latency (SOL) did not vary significantly in the two groups, but subjective SOL was higher in POTS patient (56 ± 66 min vs. 13 ± 9 min; P = 0.001). In POTS patients, there was a significant correlation between subjective complaints of tiredness and actigraphic sleep efficiency (Rs = − 0.36; R² = 0.15; P = 0.01), significant correlations between actigraphic SOL and upright norepinephrine levels (P = 0.040), and between wake after sleep onset and standing heart rate (P = 0.02).

Conclusions

POTS patients have more sleep-related symptoms and poor sleep efficiency. The pattern of subjective vs. objective SOL mismatch is suggestive of sleep-state misperception. High norepinephrine correlated with actigraphic SOL, and this activation of the stress system may contribute significantly to a hyperarousal state with consequent insomnia, poor mental and physical health in POTS patients.     

La myasthénie associée aux thymomes : particularités cliniques et résultats chirurgicaux

Objective

The aim of this study was to compare the characteristics of myasthenic patients with and without thymoma, and the results of thymectomy in both types of patients.

Material and methods

A retrospective study was conducted among 66 patients who underwent thymectomy for myasthenia gravis in our department over a 10-year period (2000–2010). The surgical approach was sternotomy or anterolateral thoracotomy. Patients were divided into two groups according to the presence of thymoma: with (T-MG) and without (NT-MG) thymoma. Complete stable remission (CSR) was the primary endpoint.

Results

Median age was 35.09 ± 9.89 years. The NT-MG group had 38 patients (57.57%) and the T-MG group 28 patients (42.43%). There was no difference between the two groups regarding the surgical approach (P = 0.52). T-MG patients were older (40.54 ± 15.16 vs. 31.37 ± 9.46) (P = 0.008) and predominantly male. There were more generalized forms (P = 0.01) and more bulbar involvement (P = 0.02) in the T-MG group. The rate of CSR at 5 years was 7% and 17% in the T-MG and NT-MG patients respectively (P = 0.70). At 10 years, it was 36% and 94.73% respectively (P = 0.03).

Conclusion

Thymomatous myasthenia gravis is characterized by the severity of its clinical features. Remission rate at 10 years was significantly lower in the myasthenia with thymoma group.     

Safety and long-term efficacy of endovascular treatment of small posterior communicating artery aneurysms by coiling with or without stent: A single center retrospective study

Objectives

Endovascular stents have been widely used in intracranial aneurysm embolization. In this work, we compared the safety and long-term efficacy of stent-assisted coiling with those of conventional coiling for small posterior communicating artery aneurysms, aiming at a better understanding of the related safety and efficacy profiles.

Methods

Between January 2008 and December 2011, 114 small PcomA aneurysms (defined as 3 mm ≤ maximum diameter < 10 mm in this study) in 108 patients were treated by endovascular treatment in our department. Patient demographics, aneurysm characteristics, angiographic results (initial and follow-up), and procedural complications were assessed.

Results

Embolization was successfully performed in all the patients. Complications occurred in 7.4% of patients in both groups. There was no associated mortality. Based on initial post-procedural angiography, the rate of complete aneurysm occlusion, neck remnant and residual sac in the stented group were 37.9%, 24.1%, and 37.9%, while in the conventional group the figures were 42.9%, 48.2%, and 8.9%, respectively. The initial angiographic results were significantly better in the conventional group, compared with the stented group (P = 0.038). The follow-up results showed that the rate of improvement in the stented group was significantly higher (53.3% vs. 14.0%; P < 0.001) and the recurrence rate was significantly lower than that in the conventional group (4.4% vs. 3.02%; P = 0.001).

Conclusion

Compared with conventional coiling, stent-assisted coiling of the small posterior communicating artery aneurysms does not increase the risk. Stents bear an advantage in reducing the recurrence rate, increasing progressive occlusion rate, and improving long-term prognosis in endovascular treatment of intracranial aneurysms.     

Concomitant and adjuvant temozolomide of newly diagnosed glioblastoma in elderly patients

Objective

The effect of concomitant and adjuvant temozolomide in glioblastoma patients above the age of 65 years lacks evidence. However, after combined treatment became standard at our center all patients were considered for combined therapy. We retrospectively analyzed the effect of temozolomide focused on elderly patients.

Methods

293 patients with newly diagnosed glioblastoma treated single-centered between 1998 and 2010, by radiation alone or concomitant and adjuvant radiochemotherapy, were included. Treatment groups were analyzed by multi- and univariate analysis. Matched pairs for age, by a 5-year-caliper, extent of resection and general state was generated for all patients and elderly subgroups.

Results

103 patients received radiation only and 190 combined treatment. Multivariate and matched pair analysis revealed a benefit due to combined temozolomide (HR 1.895 and 1.752, respectively). For patients older than 65 years median survival was 3.6 (95% CI 3.2–4.7) and 8.7 months (6.3–11.8) for radiotherapy only and combined treatment (HR 3.097, p < 0.0001, n = 90). Over the age of 70 and 75 years median survival was 3.2 (2.3–4.2) vs. 7.5 (5.1–10.9, HR 4.453, p < 0.0001, n = 62) and 3.2 (1.4–3.9) vs. 9.2 months (4.7–13.5; HR 9.037, p < 0.0001, n = 24), respectively. In 8/56 (14%) patients over the age of 70 years temozolomide was terminated due to toxicity.

Conclusion

Retrospective matched pair analysis gives class 2b evidence for prolonged survival due to concomitant and adjuvant temozolomide in elderly glioblastoma patients. Until prospective data for combined radiochemotherapy in elderly patients will be available concomitant and adjuvant temozolomide therapy should not be withheld.     

The influence of timing of polysomnography on diagnosis of obstructive sleep apnea in patients presenting with acute myocardial infarction and stable coronary artery disease

Background

We aimed to determine if timing of polysomnography (PSG) influences the diagnosis of obstructive sleep apnea (OSA) in acute myocardial infarction (AMI) or stable coronary artery disease (CAD).

Methods

A total of 160 patients admitted with AMI or stable CAD were consecutively recruited for either in-hospital (n = 80) or postdischarge (n = 80) PSG.

Results

The median time from admission to PSG for the in-hospital and postdischarge groups was 1 day and 17 days, respectively (P < .001). Overall, 59 patients (36.9%) were diagnosed with OSA (apnea–hypopnea index [AHI] ?15), and they were more likely to have diabetes mellitus (DM), hypertension, hyperlipidemia, chronic renal failure, and a greater body mass index (BMI) (P < .05 for all). The diagnosis of OSA was significantly higher (P = .037) in patients who had a PSG performed as an inpatient than those who had a PSG as an outpatient. There was a significant interaction between clinical presentation and the effect of PSG timing on the diagnosis of OSA (P = .003). For the patients presenting with AMI but not those with stable CAD, in-hospital PSG was an independent predictor of OSA (adjusted odds ratio, 3.84 [95% confidence interval, 1.42–10.41]; P = .008).

Conclusion

The timing of PSG influenced the diagnosis of OSA in patients who presented with AMI but not in those who presented with stable CAD.     

Complications following cranioplasty using autologous bone or polymethylmethacrylate—Retrospective experience from a single center

Objective

A decompressive hemicraniectomy is a potentially life-saving intervention following head trauma. Once performed patients are obliged to undergo a second procedure with cranioplasty. Two of the most commonly used materials are autologous bone and polymethylmethacrylate (PMMA). We have now evaluated complications following a cranioplasty using these materials.

Materials and methods

During a 7-year period (2002–2008) 49 patients were operated with a decompressive craniectomy following head trauma. Patients received a cranioplasty consisting of autologous bone (30 patients, 61.2%) or PMMA (19 patients, 38.8%) and were followed at least 24 months. Patient data were collected retrospectively.

Results

Twenty patients (20/49, 40.8%) experienced a complication that prompted a re-operation. There was a significantly higher rate of complications leading to a re-operation (53.3% vs. 21.1%, p = 0.03) and a shorter survival time of the cranioplasty (mean 48.1 ± 7.8 vs. 79.5 ± 9.0 months, p = 0.035) in patients with autologous bone compared to PMMA. Bone resorption and the presence of postoperative hematomas were significantly more common in patients with autologous bone. The material used for cranioplasty was the only variable that significantly correlated to the rate of complications.

Conclusions

In our series we had a high percentage of patients needing re-operation due to complications following a cranioplasty. Though generally considered a straightforward procedure, complications and associated morbidity in patients undergoing cranioplasty should not be underestimated.     

Association between PAI-1 4G/5G Polymorphisms and osteonecrosis of femoral head: A Meta-analysis

Background

The polymorphism of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been correlated with susceptibility to osteonecrosis of the femoral head (ONFH), but study results are controversial. The aim of this study was to derive a more precise estimation of the relationship between the PAI-1 4G/5G Gene polymorphism and ONFH by performing a meta-analysis.

Methods

The meta-analysis was based on five eligible case-control studies involving 419 cases and 969 controls and summarized data indicating the association between PAI-1 polymorphism and risk of osteonecrosis of the femoral head. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to assess the strength of this association in the random-effects model or fixed-effects model.

Results

A significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G4G + 4G5G vs. 5G5G (OR = 1.766, 95% CI 1.279–2.437, P = 0.001), 4G/4G vs. 4G/5G + 5G/5G (OR = 2.050, 95% CI 1.581–2.657, P = 0.000), 4G/4G vs. 5G/5G (OR = 2.553, 95% CI 1.345–4.846, P = 0.004), and 4G vs. 5G (OR = 1.758, 95% CI 1.236–2.500, P = 0.002). No significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G/5G vs. 5G/5G (OR = 1.327, 95% CI 0.939–1.877, P = 0.109).

Conclusions

This meta-analysis suggested that 4G/5G polymorphism of the PAI-1 gene was a risk factor for ONFH. This study also suggests that the PAI-1 4G4G genotype may indicate a risk for ONFH.     

The impact of childhood trauma on depression: Does resilience matter? Population-based results from the Study of Health in Pomerania

Objective

Data suggests that traumatic experiences at early age contribute to the onset of major depressive disorder (MDD) in later life. This study aims at investigating the influence of dispositional resilience on this relationship.

Methods

Two thousand and forty-six subjects aged 29–89 (SD = 13.9) from a community based sample who were free of MDD during the last 12 months prior to data collection were diagnosed for Lifetime diagnosis of MDD by the Munich-Composite International Diagnostic Interview (M-CIDI) according to DSM-IV criteria. Childhood maltreatment (CM) and resilience were assessed with the Childhood Trauma Questionnaire (CTQ) and the Resilience-Scale (RS-25).

Results

Both CM (OR = 1.03, 95% CI [1.02, 1.04], P < .000) and resilience (OR = 0.98, 95% CI [0.98, 0.99], P < .000) were associated with MDD later in life. The detrimental effects of low resilience on MDD were not only especially prominent in subjects with a history of CM (OR = 3.18, 95% CI [1.84, 5.50], P < .000), but also effective in subjects without CM (OR = 2.62, 95% CI [1.41, 4.88], P = .002).

Conclusions

The findings support the clinical assumption that resilient subjects may be partly protected against the detrimental long-term effects of child abuse and neglect.     

Association of depression symptoms with quality of life and chronic artery vasculopathy: A cross-sectional study in heart transplant patients

Objective

Depression represents a relevant co-morbidity in patients with chronic heart disease and may diminish the overall success for long-term survival after heart transplantation (HTx). This study aimed to assess the prevalence of depression symptoms in long-term HTx survivors, and to compare depressive patients to those without depression with respect to chronic artery vasculopathy (CAV).

Methods

A sample of 203 HTx patients, median 11.5 (IQR 7–17) years after transplant, provided detailed data of depression symptoms, and other psychosocial symptoms including anxiety, family support, professional re-integration, and health-related quality of life (HRQoL). Data were analyzed for an association with CAV.

Results

Overall, 14.8% patients (95% CI: 10.2–20.4) showed relevant depression symptoms. No significant differences were seen between non-depressed vs. depressed patients with respect to demographics, clinical variables, and cardiovascular risk factors. Anxiety was prevalent in 9.0% (95% CI: 5.4–13.9) of the sample. Depression symptoms showed impaired HRQoL in the SF-36 physical (P = .012) and psychosocial (P = .0001) components. CAV was prevalent in 34.0% (95% CI: 27.5–41.0), and depression symptoms and CAV were not significantly associated. CAV-patients did not report their physical HRQoL being lower relative to those without CAV (P = .40). Multivariate analysis revealed overweight BMI (OR = 2.20; P = .04), longer time since transplant (OR = 1.10; P = .001), and older age (OR = 1.04; P = .01) being associated with CAV.

Conclusion

Depression symptoms are prevalent in long-term survivors after HTx, and psychological impairments decrease patients' perceptions of HRQoL. More research seems necessary to identify the inter-relationship between depression symptoms and CAV, in order to develop targeted interventions to overcome this problem.     

Role of prophylactic filter placement in the endovascular treatment of symptomatic thrombosis in the central veins

Objectives

To evaluate the role of filter implantation in reducing the incidence of fatal pulmonary embolism during the endovascular treatment of thrombosis in the major tributary of the superior vena cava (SVC).

Methods

From October 2004 to October 2008, we conducted a cohort study of 40 patients with thrombosis of the central veins who were preparing for endovascular interventions and received or did not receive filter. The symptom scores were measured, the incidence of pulmonary embolism (PE) was observed, and patient follow-up studies were conducted for three years.

Results

One week after therapy, the symptom score improved in both groups compared with before therapy (P < 0.001), but no significant difference was found between the scores of the two groups (P > 0.05). Four patients in the control group died from PEs after therapy, but no patients in the filter group presented evidence of PE. The survival rates at 1, 2, and 3 years (72.9%, 50%, and 27.1%, respectively) for the filter group were higher than those for the control group (47.6%, 19.0% and 14.3%, respectively; P = 0.015). The survival time of patients in the filter group with bronchogenic carcinoma (18 ± 2 months) was longer than that of the patients in the control group (12 ± 2 months) after the endovascular treatment (P < 0.001).

Conclusions

Prophylactic filter placement could be a safe and effective method for preventing PE in pre- or post-endovascular-treated patients with thrombi in their central veins.     

Intravenous rt-PA in patients with ischaemic stroke and renal dysfunction

Objective

Renal dysfunction (RD) increases risk for ischaemic stroke (IS). The impact of RD on the effects of iv-thrombolysis in the Caucasian population has not been fully determined.

Aims

To evaluate the associations between RD and the outcome of iv-thrombolysis in Caucasian patients with IS.

Methods

The observational, multicentre study included 404 patients with IS who were treated with iv-thrombolysis. RD was defined as estimated glomerular filtration rate ≤60 ml/min/1.73 m². Outcome was assessed with modified Rankin Score at 3 months after the stroke onset.

Results

Medians baseline NIHSS score did not differ between groups of patients with and without RD (12.0 vs. 11.0 pts, p = 0.33). Unfavourable outcome was found in 52.1% of patients with and in 41.2% of patients without RD (p = 0.05), mortality was higher in patients with RD (29.9% vs. 14.3%, p < 0.001), and the presence of haemorrhagic transformation (HT) did not differ between the groups (17.1% vs. 17.1% respectively, p = 0.996). A multivariate analysis showed no impact of RD on the unfavourable outcome (OR 0.98; 95%CI 0.88–1.10), mortality (OR 0.92; 95%CI 0.81–1.05) or presence of HT (OR 1.03; 95%CI 0.90–1.18).

Conclusions

We found no impact of RD on the safety and efficacy of iv-thrombolysis in Caucasian patients with IS.     

Intracerebral metastases of malignant melanoma and their recurrences—A clinical analysis

Introduction

Brain metastases (BM) commonly occur in patients with metastatic malignant melanoma (MM). Prognosis is poor even with maximal therapy. The aim of the current study was to retrospectively evaluate patients with BM of MM who were treated neurosurgically with respect to clinical presentation, recurrent disease, survival and factors affecting survival.

Patients and methods

Thirty-four patients (19 f/15 m) with BM of MM were treated in our hospital between 2000 and 2010. Patient data were analysed, survival was examined using Kaplan–Meier-estimates and factors affecting prognosis were evaluated using uni- and multivariate analysis.

Results

Twenty-two patients (64.7%) had a single BM, whereas twelve patients (35.3%) revealed two or more lesions. Median survival for patients with a single BM was 13.0 months (95%-CI 9.3–16.7 months), this was significantly (p = 0.014) better than for patients with two or more BM (median 5.0, 95%-CI 3.4–14.6 months).Nineteen patients (55.9%) developed an intracranial relapse after microsurgical resection of a first lesion. Patients with an isolated intracerebral relapse survived significantly (p = 0.003) longer than those with systemic progression (median 6.0, 95%-CI 0.0–15.3 months vs median 3.0, 95%-CI 1.7–4.3 months). Similarly, patients with a high performance status showed significantly (p = 0.001) prolonged survival (median 7.0, 95%-CI 0.0–19.9 months vs median 1.0, 95%-CI 0.0–2.2 months). Eleven out of nineteen patients (57.9%) underwent either another microsurgical resection (n = 6) or stereotactic radiosurgery (n = 5). These patients remained on a high performance status even after aggressive therapy.

Discussion

Even though the prognosis for patients with BM of MM is generally poor, patients with a single BM can benefit from microsurgical resection. However, there is a high risk of intracranial relapse. In selected patients with a good performance status and recurrent intracranial disease, recurrent local therapy can be justified and useful.     

Increased factor XIa levels in patients with a first acute myocardial infarction: The introduction of a new thrombin generation based factor XIa assay

Objective

One of the contributing mechanisms in acute myocardial infarction (AMI) is plasma hypercoagulability. Recently, it was suggested that factor XI activation might play a role in atherothrombosis. To quantify factor XIa plasma levels, we developed a new thrombin generation based assay and hypothesized that in AMI patients factor XIa levels are increased during the acute thrombotic event.

Methods

A prospective cohort study was performed including 56 patients with first AMI. Blood was collected upon admission and after 6 months. Reference blood samples were obtained from 30 apparently healthy control subjects. Plasma samples were diluted (1:5) in factor XI deficient plasma and factor XIa plasma levels were established using a reference curve (0-12.5 pM factor XIa) and an inhibitory anti-factor XIa antibody. The established FXIa concentrations were related to the 1-year outcome.

Results

Factor XIa plasma concentrations were significantly increased in AMI patients on admission compared to 6 months after the event (3.7 pM [2.7-5.5] vs. 2.8 [1.9-4.3], median ± IQR; P = 0.001) and compared to healthy controls (3.7 pM [2.7-5.5] vs. 2.7 [1.6-4.2], median ± IQR; P = 0.004). However, a high factor FXIa level at baseline was not significantly associated with a recurrent cardiovascular event (OR 1.26, 95%CI 0.33-4.7).

Conclusions

This study presents the first application of a new thrombin generation based factor XIa assay, showing significantly increased factor XIa levels in AMI patients on admission compared to 6 months after the event and compared to healthy controls. The factor XIa concentration was not associated with the risk of recurrence.     

Occurrence and recurrence of spontaneous chronic subdural haematoma is associated with a factor XIII deficiency

Objective

In some patients, chronic subdural haematoma (cSDH) appears to occur spontaneously with frequent re-bleeding events. The pathophysiology of this phenomenon is still poorly understood. Because coagulation factor XIII (FXIII) is known to be involved in vascular integrity, endothelial barrier function and wound healing, we evaluated the role of FXIII in spontaneous cSDH.

Methods

We prospectively scrutinised the origin of cSDH in 117 patients and identified a subgroup of patients suffering from spontaneous cSDH who were included in this study. We analysed the plasma activity of FXIII and standard coagulation parameters and compared these data to age- and sex-matched healthy controls. We assessed the occurrence of re-bleeding events using clinical and imaging data and compared FXIII activity in patients with and without re-bleeding events.

Results

Out of 117 cSDH patients, 18 individuals suffered from spontaneous cSDH in this study. The patients with spontaneous cSDH showed significantly lower FXIII activity than the control group (65% [52.75, 80.25] (median [IQR]) vs. 93% [81, 111], P = 0.001), whereas standard coagulation parameters did not differ significantly between the groups. Six patients developed re-bleeding events after haematoma evacuation, and these patients expressed significantly lower FXIII activity compared to the other 12 patients (47.5% [33.5, 64] vs. 78.5% [58, 87], P = 0.005). The patient group with FXIII ≤ 68.5% differed significantly from the group with FXIII > 68.5% when categorised by the occurrence of re-bleeding events (n = 6/9 vs. n = 0/9, P = 0.009). This cut-off value predicted the re-bleeding events with a sensitivity of 100% and a specificity of 75% (positive predictive value: 66%, negative predictive value: 100%).

Conclusion

FXIII deficiency may play a pathophysiological role in spontaneous cSDH, so we suggest investigating FXIII activity because it may predict re-bleeding events after treatment. In individuals with considerably low FXIII activity, FXIII substitution may mitigate the chronic nature of this disease.     

Relationships between IGF-1, schizophrenia,and treatment of metabolic syndrome

Objectives

The use of atypical antipsychotic drugs in patients with psychiatric illness may result in dyslipidemia, hypertension, glucose intolerance, and abdominal obesity, which are together referred to as metabolic syndrome (MS). To investigate any correlations among insulin-like growth factor-1 (IGF-1), schizophrenia, and MS, we examined the metabolic profiles of patients with schizophrenia taking atypical antipsychotics.

Design

Patients with schizophrenia, their siblings, and controls participated in this study (N = 50 in each group). The Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID I) and the Brief Psychiatric Rating Scale (BPRS) were administered to patients, and SCID I was administered to patients' siblings. We drew blood to measure IGF-1 levels and to determine the metabolic profiles of all participants; we also conducted anthropometric measurements.

Results

There were no significant differences in IGF-1 levels between groups. By comparing IGF-1 levels with MS-related parameters, we found that IGF-1 levels were negatively correlated with triglyceride levels in the control group, and positively correlated with HDL levels in the patient group (Pearson's correlation: r = −0.291, P = 0.04, and r = 0.328, P = 0.02, respectively). Compared to their siblings, patients with schizophrenia had a significantly different body mass index, waist circumference, and insulin resistance, and showed a trend toward a difference in glucose levels (ANOVA: P = 0.004, P < 0.0001, P = 0.004, P = 0.072, respectively).

Conclusion

A correlation between IGF-1 and MS may significantly influence future therapeutic strategies for MS. In order to determine the role of IGF-1 in schizophrenia, comprehensive longitudinal studies with first-episode drug-naive patients are needed.     

Clinical outcome of surgically treated low-grade gliomas: A retrospective analysis of a single institute

Objective

Low grade gliomas (LGGs) are slow-growing primary brain tumors with heterogeneous clinical behaviors. The aim of our study is to review the treatment outcome of 63 patients with LGGs focusing on surgical outcome and the current therapeutic strategy.

Methods

We retrospectively enrolled 63 patients surgically treated for LGGs. The gross total resection (GTR) was performed in 35 patients (60.3%), subtotal resection (STR) was performed in 19 patients (31.7%) and partial resection (PR) or biopsy was performed in 9 patients (14.3%). We analyzed their progression-free survival (PFS), overall survival (OS), and malignant transformation with regard to age, gender, Karnofsky performance score (KPS), clinical presentation, tumor location, radiologic pattern, contrast enhancement, extent of removal, pathologic subtype, chemotherapy (CT) and radiotherapy (RT) treatment.

Results

Among all LGGs, the 3-year OS rate was 80% and the 5-year OS was 76%. The 3-year PFS rate was 83.6% and the 5-year PFS was 25%. The non-eloquent area location showed a longer PFS than the eloquent area location (p = 0.05). Oligodendroglial pathology showed a longer PFS compared to oligoastrocytomas and astrocytomas (p = 0.02). Patients older than 60 years had poorer OS than younger patients (p < 0.05). Female gender had a shorter OS than male gender (p < 0.05), and a KPS of 90 or 100 had a longer OS than a KPS of 80 (p < 0.05). Oligodendroglial pathology statistically correlated with a longer OS (p < 0.05).

Conclusion

The findings from our study, which were confirmed by uni- and multivariate analyses, demonstrated that radical tumor resection was associated with better long-term outcomes and tumor progression for patients with LGG.