Ultrasound-based real-time neuronavigated fluorescence-guided surgery for high-grade gliomas: technical note and preliminary experience.

BACKGROUND: The extent of resection (EOR) plays a fundamental role in the prognosis of patients with high-grade gliomas (HGG). One of the main challenges in achieving a complete resection is the distinction between tumor and normal brain. Nowadays, several technologies are employed to obtain a higher tumor removal rate and respect the normal tissue in glioma surgery and in the last decades, fluorescein sodium (FS) and intraoperative ultrasound (IOUS) have been widely used. The aim of our technical note is to demonstrate how combining these two tools offers an ultrasound-based real-time neuronavigated fluorescence-guided surgery in order to optimize HGG removal. METHODS: Five patients (3 males, 2 females; mean age 55.2 years, range 36-68 years) undergoing craniotomies for removal of intraaxial lesions suggestive of high-grade gliomas on preoperative MRI were included in the study. Intraoperative navigated B-mode and CEUS associated with sodium fluorescein were used in all cases; white light appearance, IOUS, and fluorescence findings were recorded immediately after each surgery. Also, extent of resection was evaluated on postoperative Gd-enhanced MRI performed within 72 h. RESULTS: All tumors effectively stained yellow with fluorescein sodium during the surgical procedure and four were well delineated by IOUS. IOUS was repeated frequently (average 2.6 time) to obtain an orientation of the gross residual tumor with respect to anatomical landmarks as the surgery proceeded. Tumor removal was completed under Yellow 560 filter. CONCLUSIONS: In our technical report, we demonstrate that combining intraoperatively fluorescein sodium and IOUS improves the information and facilitates making decisions during the HGG surgery. Further experience gained in larger studies will help confirm these findings.

Skull Bone Defects Reconstruction with Custom-Made Titanium Graft shaped with Electron Beam Melting Technology: Preliminary Experience in a Series of Ten Patients.

BACKGROUND: Cranioplasty represents a challenge in neurosurgery. Its goal is not only plastic reconstruction of the skull but also to restore and preserve cranial function, to improve cerebral hemodynamics, and to provide mechanical protection of the neural structures. The ideal material for the reconstructive procedures and the surgical timing are still controversial. Many alloplastic materials are available for performing cranioplasty and among these, titanium still represents a widely proven and accepted choice. METHODS: The aim of our study was to present our preliminary experience with a "custom-made" cranioplasty, using electron beam melting (EBM) technology, in a series of ten patients. EBM is a new sintering method for shaping titanium powder directly in three-dimensional (3D) implants. FINDINGS: To the best of our knowledge this is the first report of a skull reconstruction performed by this technique. In a 1-year follow-up no postoperative complications have been observed and good clinical and esthetic outcomes were achieved. CONCLUSION: Costs higher than those for other types of titanium mesh, a longer production process, and the greater expertise needed for this technique are compensated by the achievement of most complex skull reconstructions with a shorter operative time.

Porous titanium microsphere kyphoplasty for augmentation treatment of osteoporotic vertebral fractures: Technical report and case series.

Background: Vertebral augmentation procedures (VAPs) are used in cases of persistent and unresponsive pain in patients with vertebral compression fractures (VCFs). Although VAPs are considered a safe procedure providing quick pain relief and improved physical function, some postoperative complications can occur, for example, bone cement leakage. The material used in this procedure is almost exclusively polymethyl methacrylate (PMMA), which appears to lack biological activity and osteointegration capabilities. In this study, we introduce a new filling system consisting of cannulas preloaded with titanium microspheres, which stabilizes and consolidates the structure of the vertebral body in treating VCFs after the performance of the kyphoplasty procedure. Methods: We report a retrospective case series of six patients affected by osteoporotic vertebral fractures with worsening back pain, neurologic impairment, and failed conservative treatment who underwent the VAP at our institute, for which the SPHEROPLAST [MT ORTHO s.r.l., Aci Sant'Antonio (CT), Italy] system was used. Results: The patients had failed an average conservative trial of 3.9 weeks before they presented to us with neurodeficit. There were two men and four women with a mean age of 74.5 years. The average hospital stay was 2 days. There were no reported perioperative complications related to cement injection, such as intraoperative hypoxia, hypotension, pulmonary embolization, myocardial infarction, neurovascular or viscera injury, or death. The VAS score significantly decreased from a mean preoperative of 7.5 (range 6-19) to 3.8 (range 3-5) immediately after surgery and 1.8 (range 1-3). Conclusion: We report the first clinical results in a series of six patients treated for VCF using the microsphere system after analyzing the clinical results produced by, and the complications that arose from, this new device. In patients with VCF, the VAP using titanium microspheres appears to be a feasible and safe procedure with a low risk of material leakage.

Reconstruction of vertebral body in thoracolumbar AO type A post-traumatic fractures by balloon kyphoplasty: a series of 85 patients with a long follow-up and review of the literature.

BACKGROUND: Traumatic fractures of the thoracolumbar spine are common injuries, accounting for approximately 90% of all spinal traumas. Optimal management of these fractures still gives rises to much debate in the literature. Currently, one of the treatment options in young patients with stable traumatic vertebral fractures is conservative treatment using braces. Kyphoplasty as a minimally invasive procedure has been shown to be effective in stabilizing vertebral body fractures, resulting in immediate pain relief and improving physical function with early return to work activity. The aim of our study was to report VAS, ODI scores, and kyphosis correction following treatment. METHODS: This is a retrospective study to investigate the clinical and radiological results 10 years after percutaneous balloon kyphoplasty followed by cement augmentation with polymethylmethacrylate (PMMA) or calcium phosphate cements (CPC), according to age, in 85 consecutive patients affected by 91 AO spine type A traumatic fractures of the thoracolumbar spine (A1, A2, and A3). Clinical follow-up was performed with the Visual Analogic Scale (VAS) at the preoperative visit and in the postoperative follow-up after 1 week, 1, 6, 12 months, and each year up to 10 years. Additionally, the Oswestry Disability Index (ODI) improvement was calculated as the difference between the ODI scores at the preoperative visit and at final follow-up. Finally, the Cobb angle from this cohort was assessed before surgery, immediately postoperatively, and at the end of follow-up. RESULTS: Kyphoplasty markedly improved pain and resulted in statistically significant vertebral height restoration and normalization of morphologic shape indexes that remained stable for at least 10 years following treatment. CONCLUSIONS: The present study showed that kyphoplasty and cement augmentation are an effective method of treatment for selected type A fractures.

Obesity and Circulating Levels of Vitamin D before and after Weight Loss Induced by a Very Low-Calorie Ketogenic Diet.

Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10-12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass-kg (r = -0.40; p < 0.05) and body mass index (r = -0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass-kg (r = -0.43; p < 0.01). Conclusion: This study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss.

Influence of Habitual Dairy Food Intake on LDL Cholesterol in a Population-Based Cohort.

BACKGROUND: Cholesterol has a pivotal role in human physiology, exerting both structural and functional activity. However, higher blood cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), are a major cardiovascular risk factor. Therefore, special attention has been given to the effect of dietary factors in influencing LDL-C blood levels. In particular, much research has focused on dairy products, since they are a main component of different dietary patterns worldwide. A large body of evidence did not support the hypothesis that dairy products significantly increase circulating LDL-C, but no definitive data are available. Hence, we aimed to assess the relationships among LDL-C, habitual dairy food intake and anthropometric variables in a cohort representative of the general population in a Mediterranean area. METHODS: We evaluated 802 healthy adults included in the ABCD_2 (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. The habitual intake of dairy products was assessed with a validated food frequency questionnaire, and LDL-C serum levels and several anthropometric parameters were measured. RESULTS: The group with high LDL-C serum concentrations (≥130 vs. <130 mg/dL) exhibited higher age, body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage, systolic and diastolic blood pressure, carotid intima-media thickness and glycated hemoglobin. The habitual diet was not different between the groups in terms of macronutrient, cholesterol, egg and dairy food intake, with the exception of the weekly number of portions of milk (higher in the low LDL-C group vs. the high LDL-C group) and ricotta cheese (higher in the high LDL-C group vs. the LDL-C group). No significant correlation was found between LDL-C blood levels and the habitual intake of dairy products or the dietary intake of cholesterol and fats. The multivariate regression analyses (R2 = 0.94) showed that LDL-C blood levels were significantly associated with the habitual intake of milk (p < 0.005) and ricotta cheese (p < 0.001) and with BMI (p < 0.001). CONCLUSION: Our study reported that total dairy food consumption was not correlated with LDL-C blood levels. However, multivariate analyses showed an inverse association between serum LDL-C and milk intake as well as a positive association between ricotta cheese intake and LDL-C concentrations. More studies are needed to better characterize the relationship between dairy products and circulating LDL-C.

Clinical Use of κ Free Light Chains Index as a Screening Test for Multiple Sclerosis.

OBJECTIVE: To assess the usefulness of the κ free light chain index (κFLCi) as a screening test to identify patients with suspected MS. METHODS: The study included 56 patients with a request to test for oligoclonal bands (OCBs). OCBs were detected by isoelectric focusing, followed by immunofixation. Cerebrospinal fluid (CSF) and serum κFLC were measured by a turbidimetric assay. Also, the κFLC index (κFLCi) was calculated. RESULTS: CSF κFLC levels and κFLCi were significantly higher in patients with multiple sclerosis (MS) than in patients with other neurological diseases (NDs; P < .001 and P < .001, respectively). At the cutoff value of 2.9, the κFLCi detected MS with sensitivity of 97% and specificity of 65%. Overall, 92% patients with κFLCi of 2.9 or greater and who had tested positive for OCBs were diagnosed as having MS. CONCLUSION: Our findings support the use of κFLCi as a screening test when MS is suspected, followed by OCB detection as a confirmatory test for the diagnosis of MS.

Aneurysm clipping following endovascular coil embolization: a report of two cases.

BACKGROUND: Treatment of intracranial aneurysms by Guglielmi detachable coil (GDC) embolization is a useful therapeutic alternative to surgery. This procedure is attractive as a minimally invasive approach to treat cerebral aneurysms; however, is not devoid of complications or failure and retreatment, with either a surgical or endovascular technique, may often be required. CASE REPORTS: Two cases are presented in which surgery was required after coil embolization. In one case, surgical treatment was performed one month later because of regrowth and subsequent bleeding of the aneurysm. In the second case, surgical treatment was carried out six months later because of recanalization of the vascular malformation. Surgical treatment excluded both aneurysms from the cerebral circulation. CONCLUSIONS: In this paper the authors illustrate their experience and underline the difficulty of aneurysm surgery with coils in place.

Chronic inflammation causing spinal cord compression in human immunodeficiency virus infection.

BACKGROUND: The incidence of central nervous system involvement has increased in the setting of acquired immune deficiency syndrome (AIDS). Although rarely reported, spinal cord compression, in the setting of AIDS, has been associated with primary lymphoma or opportunistic infections. CASE REPORT: The authors describe the case of a young man who was admitted to our institution with rapid and progressive paraplegia. Imaging studies revealed an extramedullary lesion compressing the spinal cord spanning 3 thoracic levels. Surgical treatment was performed, and the compressing process completely excised. Histologic examination of the lesion showed a chronic inflammatory tissue with many necrotic areas without signs of infection or lymphoma. The patient progressively regained normal strength in his legs and was discharged home. CONCLUSIONS: In patients with HIV, chronic inflammation can lead to a lesion that compresses the spinal cord and should be considered in the differential diagnosis. Knowledge of this entity gains importance with the increasing incidence of HIV because timely excision can restore neurologic deficits. This condition may be considered a new clinical entity, the true incidence of which will be established using the diagnostic protocols provided and further case reports.

Immunohistochemical study of the extracellular matrix proteins laminin, fibronectin and type IV collagen in secretory meningiomas.

The extracellular matrix plays a pivotal role in numerous cellular functions during normal and pathological processes. Secretory meningiomas are rare histological meningioma subtypes that have benign behavior, are highly vascularized and are frequently accompanied by massive peritumoral edema. The aim of this study was to assess in secretory meningiomas the immunohistochemical expression of laminin, fibronectin and type IV collagen, proteins found in the extracellular matrix. Extracellular matrix proteins were evaluated in samples from six secretory meningiomas using a semiquantitative scale ranging from not detected (0) to marked (3). Laminin expression was not detected in two cases, but was minimal in one, moderate in one and marked in the remaining cases. Fibronectin expression was absent in two cases, minimal in two, moderate in one and marked with generalized distribution in the remaining case. Type IV collagen expression was minimal in three cases, moderate in two and marked with generalized distribution in the remaining case. Our results are indicative of significant neoangiogenic activity. Meningiomas increase in size through increased production of extracellular matrix; furthermore, the proliferation of cells typically associated with neoplasia requires considerable interaction with the extracellular matrix.

New Hope in Brain Glioma Surgery: The Role of Intraoperative Ultrasound. A Review.

Maximal safe resection represents the gold standard for surgery of malignant brain tumors. As regards gross-total resection, accurate localization and precise delineation of the tumor margins are required. Intraoperative diagnostic imaging (Intra-Operative Magnetic Resonance-IOMR, Intra-Operative Computed Tomography-IOCT, Intra-Operative Ultrasound-IOUS) and dyes (fluorescence) have become relevant in brain tumor surgery, allowing for a more radical and safer tumor resection. IOUS guidance for brain tumor surgery is accurate in distinguishing tumor from normal parenchyma, and it allows a real-time intraoperative visualization. We aim to evaluate the role of IOUS in gliomas surgery and to outline specific strategies to maximize its efficacy. We performed a literature research through the Pubmed database by selecting each article which was focused on the use of IOUS in brain tumor surgery, and in particular in glioma surgery, published in the last 15 years (from 2003 to 2018). We selected 39 papers concerning the use of IOUS in brain tumor surgery, including gliomas. IOUS exerts a notable attraction due to its low cost, minimal interruption of the operational flow, and lack of radiation exposure. Our literature review shows that increasing the use of ultrasound in brain tumors allows more radical resections, thus giving rise to increases in survival.

With a Little Help from My Friends: The Role of Intraoperative Fluorescent Dyes in the Surgical Management of High-Grade Gliomas.

High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA) is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX) is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS), on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB) areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO) but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients.

Preliminary Experience with a Novel System of Facet Fixation to Treat Patients with Lumbar Degenerative Disease. A New Perspective in Minimally Invasive Spine Surgery?

PURPOSE: We report our experience with a novel surgical device for the treatment of lumbar degenerative microinstability. Facet Wedge (DePuy Synthes, Raynham, Massachusetts, United States) is a novel technique of intra-articular lumbar facet fixation that provides a minimally invasive alternative to standard posterior fixation. MATERIALS AND METHODS: From November 2014 to July 2015, 38 patients underwent single-level Facet Wedge implantation. The main surgical indications included herniated disk (18 patients), spinal canal and foraminal stenosis (14 patients), and Meyerding grade I degenerative spondylolisthesis (6 patients). All the patients showed radiologic signs of microinstability: hyperintensity in both facet joints (facet fluid signal) in T2-weighted magnetic resonance imaging and a black disk as a sign of degenerative disease. No slippage was evident at dynamic radiograph. After a period of conservative treatment (minimum of 6 months), surgery was performed. All patients' follow-up lasted over at least 12 months. RESULTS: The low back visual analog scale score decreased significantly after surgery (from an average of 8.2 to 3.1 at final follow-up). Postoperatively, the Oswestry Disability Index showed a significant reduction (14.7 on average). No slippage or signs of adjacent segment degeneration was detected in neuroimaging follow-up. CONCLUSION: Facet Wedge allows facet fixation in lumbar degenerative microinstability. To the best of our knowledge, this is the first clinical series reported in the literature on this novel device.

NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat.

Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectrophotofluorimetric technique 2 days post-injury). Animals were injected with 400 muL of autologous blood into the cisterna magna. Within 5 min, rats received daily oral administration of FBM (15, 30, or 45 mg/kg) for 2 or 5 days. Results were compared with sham-injured controls treated with oral saline or FBM (15, 30, or 45 mg/kg). FBM administration significantly ameliorated SAH-related changes in Beam Balance scores on days 1 and 2 and Beam Balance time on days 1-3, Beam Walking performance on days 1 and 2, and Body Weight on days 3-5. FBM also decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices; subcortical and cerebellar gray matter; and brainstem. This study demonstrates that, in terms of behavioral and microvascular effects, FBM is beneficial in a dose-dependent manner after experimental SAH in rats. These results reinforce the concept that NMDA excitotoxicity is involved in the cerebral dysfunction that follows SAH.

The role of erythropoietin in neuroprotection: therapeutic perspectives.

Nervous system diseases are very complex conditions comprising a large variety of local and systemic responses. Several therapeutic agents interfering with all or in part the biochemical steps that ultimately cause neuronal death have been demonstrated to be neuroprotective in preclinical models. However, all the agents so far investigated have inexorably failed in the phase III trials carried out. A large body of evidence suggests that the hormone erythropoietin (EPO), besides its well-known hematopoietic action, exerts beneficial effects in the central nervous system. EPO's effect has been assessed in several experimental models of brain and spinal cord injury thus becoming a serious candidate for neuroprotection. The use of EPO as neuroprotectant raises several questions. Besides dosage and therapeutic time window, the safety of recombinant EPO administration in the setting of nervous system diseases takes priority over all other questions. Although recombinant EPO seems to be potentially safe at the neuroprotective proved doses, cardiovascular or cerebrovascular events can occur as a result of its bone marrow stimulating activities. The successful trial using EPO in patients with ischemic stroke and the large body of experimental evidence encourages intensive evaluation of this cytokine to support safe and larger clinical trials in the near future.

Neuroprotection by erythropoietin administration after experimental traumatic brain injury.

A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. Experimental TBI was induced in rats by a cryogenic injury model. rHuEPO or placebo was injected intraperitoneally immediately after the injury and then every 8 h until 2 or 14 days. Forty-eight hours after injury brain water content, an indicator of brain edema, was measured with the wet-dry method and blood-brain barrier (BBB) breakdown was evaluated by assay of Evans blue extravasation. Furthermore, extent of cerebral damage was assessed. Administration of rHuEPO markedly improved recovery from motor dysfunction compared with placebo group (P<0.05). Brain edema was significantly reduced in the cortex of the EPO-treated group relative to that in the placebo-treated group (80.6+/-0.3% versus 91.8%+/-0.8% respectively, P<0.05). BBB breakdown was significantly lower in EPO-treated group than in the placebo-treated group (66.2+/-18.7 mug/g versus 181.3+/-21 mug/g, respectively, P<0.05). EPO treatment reduced injury volume significantly compared with placebo group (17.4+/-5.4 mm3 versus 37.1+/-5.3 mm3, P<0.05). EPO, administered in its recombinant form, affords significant neuroprotection in experimental TBI model and may hold promise for future clinical applications.

Neuroprotective potential of erythropoietin and darbepoetin alfa in an experimental model of sciatic nerve injury. Laboratory investigation.

OBJECT: The objectives of this study were to examine whether the systemic administration of recombinant human erythropoietin (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery in a rat model of sciatic nerve injury, and to compare the effects of these agents in the model. METHODS: Thirty male Sprague-Dawley rats received a crush injury to the left sciatic nerve and subsequently underwent either placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. RESULTS: Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment and improving compound muscle action potentials following nerve injury. Darbepoetin alfa, however, shortened the duration of peripheral nerve recovery'and facilitated recovery from the neurological and electrophysiological impairment following crush injury significantly better than rHuEPO. Examination of the footprint length factor data revealed that darbepoetin alfa-treated animals recovered preinjury function by postoperative Day 10, 4 days earlier than animals treated with rHuEPO and 11 days earlier than animals treated with placebo. CONCLUSIONS: These results suggest that recovery of neurological function in a model of peripheral nerve injury is more rapid with weekly administration of darbepoetin alfa than with daily rHuEPO treatment. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy. The administration of EPO in its long-lasting recombinant forms affords significant neuroprotection in peripheral nerve injury models and may hold promise for future clinical applications.

Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature.

BACKGROUND: The importance of a complete resection of high-grade gliomas (HGGs) has been highlighted in scientific literature, in order to limit tumor recurrence and above all to improve disease-free survival rates. Several fluorescent biomarkers have been tested to improve intraoperative identification of residual tumor; 5-aminolevulinic acid (5-ALA) and fluorescein sodium (FS) are now starting to play a central role in glioma surgery. We performed a retrospective analysis on 47 patients operated for HGGs. Here we report our preliminary data. METHODS: Data of 47 consecutive patients with HGG have been collected in our study (25 males, 22 females; mean age: 60.3 years, range: 27-86 years). Fluorescein (5 mg/kg of body weight) was injected intravenously right after the induction of general anesthesia. A YELLOW 560 filter was used on an OPMI Pentero 900 microscope (Carl Zeiss Meditec, Oberkochen, Germany) to complete a microsurgical tumor removal. Glioma resection and quality of life were evaluated preoperative and postoperatively. RESULTS: Gross total resection (GTR) was achieved in 53.2% (n = 25) of patients. A subtotal resection (STR) (>95%) was achieved in 29.8% (n = 14), while a partial resection (PR) (<95%) was obtained in 17% (n = 8) of patients. Overall, in 83% (n = 39) of patients who underwent fluorescence-guided surgery the resection rate achieved was >95%. No adverse effects correlated to fluorescein have been recorded. CONCLUSION: Fluorescein seems to be safe and effective in the resection of HGGs, allowing a high rate of gross total removal of contrast enhanced areas.

Amelioration of spinal cord compressive injury by pharmacological preconditioning with erythropoietin and a nonerythropoietic erythropoietin derivative.

OBJECT: Spinal cord injury (SCI) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its nonerythropoietic derivatives asialoEPO and carbamylated EPO have markedly improved functional outcome when administered after compressive SCI. However, an optimum treatment paradigm is currently unknown. Because the uninjured spinal cord expresses a high density of EPO receptor (EPOR) in the basal state, signaling through these existing receptors in advance of injury (pharmacological preconditioning) might confer neuroprotection and therefore be potentially useful in situations of anticipated damage. METHODS: The authors compared asialoEPO, a molecule that binds to the EPOR with high affinity but with a brief serum half-life (t1/2 < 2 minutes), to EPO to determine whether a single dose (10 microg/kg of body weight) administered by intravenous injection 24 hours before 1 minute of spinal cord compression provides benefit as determined by a 6-week assessment of neurological outcome and by histopathological analysis. Rats pretreated with asialoEPO or EPO and then subjected to a compressive injury exhibited improved motor function over 42 days, compared with animals treated with saline solution. However, pretreatment efficacy was substantially poorer than efficacy of treatment initiated at the time of injury. Serum samples drawn immediately before compression confirmed that no detectable asialoEPO remained within the systemic circulation. Western blot and immunohistochemical analyses performed using uninjured spinal cord 24 hours after a dose of asialoEPO exhibited a marked increase in glial fibrillary acidic protein, suggesting a glial response to EPO administration. CONCLUSIONS: These results demonstrate that EPO and its analog do not need to be present at the time of injury to provide tissue protection and that tissue protection is markedly effective when either agent is administered immediately after injury. Furthermore, the findings suggest that asialoEPO is a useful reagent with which to study the dynamics of EPO-mediated neuroprotection. In addition, the findings support the concept of using a nonerythropoietic EPO derivative to provide tissue protection without activating the undesirable effects of EPO.

Optimal duration of treatment in surgical patients with calf venous thrombosis involving one or more veins.

The aim of this study was to evaluate different durations of treatment in patients with calf venous thrombosis (CVT) involving 1 or more deep veins. The authors studied 2 groups of patients with postsurgical CVT diagnosed by echo-color Doppler. The first group consisted of 68 patients with CVT involving a single vein, and the second group consisted of 124 patients with CVT involving 2 or more veins. Immediately after diagnosis, all patients were treated with nadroparin calcium and sodium warfarin. Heparin treatment was withdrawn after 5-6 days of treatment, when the international normalized ratio (INR) was stabilized between 2 and 3. Each group was divided into 2 subgroups receiving anticoagulation treatment for 6 or 12 weeks, respectively. The endpoint was proximal extension of the thrombotic lesion, defined as the extension of the thrombus to the popliteal and/or femoral vein. In patients with single-vessel CVT there was no significant difference between the 2 subgroups, whereas in patients with CVT involving 2 or more vessels, a statistically significant difference was observed, the number of cases showing proximal extension of the thrombus being higher among patients treated for 6 weeks. Twelve weeks of anticoagulation treatment is better than 6 weeks only in patients with postsurgical CVT involving 2 or more veins.