Investigating the Potential Use of Chemical Biopsy Devices to Characterize Brain Tumor Lipidomes.

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method of enabling the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.

Metabolomic Phenotyping of Gliomas: What Can We Get with Simplified Protocol for Intact Tissue Analysis?

Glioblastoma multiforme is one of the most malignant neoplasms among humans in their third and fourth decades of life, which is evidenced by short patient survival times and rapid tumor-cell proliferation after radiation and chemotherapy. At present, the diagnosis of gliomas and decisions related to therapeutic strategies are based on genetic testing and histological analysis of the tumor, with molecular biomarkers still being sought to complement the diagnostic panel. This work aims to enable the metabolomic characterization of cancer tissue and the discovery of potential biomarkers via high-resolution mass spectrometry coupled to liquid chromatography and a solvent-free sampling protocol that uses a microprobe to extract metabolites directly from intact tumors. The metabolomic analyses were performed independently from genetic and histological testing and at a later time. Despite the small cohort analyzed in this study, the results indicated that the proposed method is able to identify metabolites associated with different malignancy grades of glioma, as well as IDH and 1p19q codeletion mutations. A comparison of the constellation of identified metabolites and the results of standard tests indicated the validity of using the characterization of one comprehensive tumor phenotype as a reflection of all diagnostically meaningful information. Due to its simplicity, the proposed analytical approach was verified as being compatible with a surgical environment and applicable for large-scale studies.

Profiling of Carnitine Shuttle System Intermediates in Gliomas Using Solid-Phase Microextraction (SPME).

Alterations in the carnitine shuttle system may be an indication of the presence of cancer. As such, in-depth analyses of this pathway in different malignant tumors could be important for the detection and treatment of this disease. The current study aims to assess the profiles of carnitine and acylcarnitines in gliomas with respect to their grade, the presence of isocitrate dehydrogenase (IDH) mutations, and 1p/19q co-deletion. Brain tumors obtained from 19 patients were sampled on-site using solid-phase microextraction (SPME) immediately following excision. Analytes were desorbed and then analyzed via liquid chromatography-high-resolution mass spectrometry. The results showed that SPME enabled the extraction of carnitine and 22 acylcarnitines. An analysis of the correlation factor revealed the presence of two separate clusters: short-chain and long-chain carnitine esters. Slightly higher carnitine and acylcarnitine concentrations were observed in the higher-malignancy tumor samples (high vs. low grade) and in those samples with worse projected clinical outcomes (without vs. with IDH mutation; without vs. with 1p/19q co-deletion). Thus, the proposed chemical biopsy approach offers a simple solution for on-site sampling that enables sample preservation, thus supporting comprehensive multi-method analyses.

Endoscopic versus stereotactic biopsies of intracranial lesions involving the ventricles.

Stereotactic biopsies of ventricular lesions may be less safe and less accurate than biopsies of superficial lesions. Accordingly, endoscopic biopsies have been increasingly used for these lesions. Except for pineal tumors, the literature lacks clear, reliable comparisons of these two methods. All 1581 adults undergoing brain tumor biopsy from 2007 to 2018 were retrospectively assessed. We selected 119 patients with intraventricular or paraventricular lesions considered suitable for both stereotactic and endoscopic biopsies. A total of 85 stereotactic and 38 endoscopic biopsies were performed. Extra procedures, including endoscopic third ventriculostomy and tumor cyst aspiration, were performed simultaneously in 5 stereotactic and 35 endoscopic cases. In 9 cases (5 stereotactic, 4 endoscopic), the biopsies were nondiagnostic (samples were nondiagnostic or the results differed from those obtained from the resected lesions). Three people died: 2 (1 stereotactic, 1 endoscopic) from delayed intraventricular bleeding and 1 (stereotactic) from brain edema. No permanent morbidity occurred. In 6 cases (all stereotactic), additional surgery was required for hydrocephalus within the first month postbiopsy. Rates of nondiagnostic biopsies, serious complications, and additional operations were not significantly different between groups. Mortality was higher after biopsy of lesions involving the ventricles, compared with intracranial lesions in any location (2.4% vs 0.3%, p = 0.016). Rates of nondiagnostic biopsies and complications were similar after endoscopic or stereotactic biopsies. Ventricular area biopsies were associated with higher mortality than biopsies in any brain area.

Sub-Perception and Supra-Perception Spinal Cord Stimulation in Chronic Pain Syndrome: A Randomized, Semi-Double-Blind, Crossover, Placebo-Controlled Trial.

BACKGROUND: The introduction of modern sub-perception modalities has improved the efficacy of spinal cord stimulation (SCS) in refractory pain syndromes of the trunk and lower limbs. The objective of this study was to evaluate the effectiveness of low and high frequency SCS among patients with chronic pain. MATERIAL AND METHODS: A randomised, semi-double-blind, placebo controlled, four period (4 × 2 weeks) crossover trial was conducted from August 2018 to January 2020. Eighteen patients with SCS due to failed back surgery syndrome and/or complex regional pain syndrome were randomised to four treatment arms without washout periods: (1) low frequency (40-60 Hz), (2) 1 kHz, (3) clustered tonic, and (4) sham SCS (i.e., placebo). The primary outcome was pain scores measured by visual analogue scale (VAS) preoperatively and during subsequent treatment arms. RESULTS: Pain scores (VAS) reported during the preoperative period was M (SD) = 8.13 (0.99). There was a 50% reduction in pain reported in the low frequency tonic treatment group (M (SD) = 4.18 (1.76)), a 37% reduction in the 1 kHz treatment group (M (SD) = 5.17 (1.4)), a 34% reduction in the clustered tonic settings group (M (SD) = 5.27 (1.33)), and a 34% reduction in the sham stimulation group (M (SD) = 5.42 (1.22)). The reduction in pain from the preoperative period to the treatment period was significant in each treatment group (p < 0.001). Overall, these reductions were of comparable magnitude between treatments. However, the modality most preferred by patients was low frequency (55% or 10 patients). CONCLUSIONS: The pain-relieving effects of SCS reached significance and were comparable across all modes of stimulation including sham. Sub-perception stimulation was not superior to supra-perception. SCS was characterised by a high degree of placebo effect. No evidence of carryover effect was observed between subsequent treatments. Contemporary neuromodulation procedures should be tailored to the individual preferences of patients.

On-Site Sampling and Extraction of Brain Tumors for Metabolomics and Lipidomics Analysis.

Despite the variety of tools available for cancer diagnosis and classification, methods that enable fast and simple characterization of tumors are still in need. In recent years, mass spectrometry has become a method of choice for untargeted profiling of discriminatory compound as potential biomarkers of a disease. Biofluids are generally considered as preferable matrices given their accessibility and easier sample processing while direct tissue profiling provides more selective information about a given cancer. Preparation of tissues for the analysis via traditional methods is much more complex and time-consuming, and, therefore, not suitable for fast on-site analysis. The current work presents a protocol combining sample preparation and extraction of small molecules on-site, immediately after tumor resection. The sampling device, which is of the size of an acupuncture needle, can be inserted directly into the tissue and then transported to the nearby laboratory for instrumental analysis. The results of metabolomics and lipidomics analyses demonstrate the capability of the approach for the establishment of phenotypes of tumors related to the histological origin of the tumor, malignancy, and genetic mutations, as well as for the selection of discriminating compounds or potential biomarkers. The non-destructive nature of the technique permits subsequent performance of routinely used tests e.g., histological tests, on the same samples used for SPME analysis, thus enabling attainment of more comprehensive information to support personalized diagnostics.

Therapeutic approach to pediatric acute mastoiditis - an update / Abordagem terapêutica da mastoidite aguda pediátrica - uma atualização

Abstract Introduction: Acute mastoiditis remains the most common complication of acute otitis media. It may rarely appear also in cochlear implant patients. However, the treatment recommendations for this disease are not precisely defined or employed, and in the current literature the differences regarding both the diagnosis and management are relatively substantial. Objective: The aim of this study was to determine a standard and safe procedure to be applied in case of pediatric acute mastoiditis. Methods: A retrospective chart review of 73 patients with 83 episodes of acute mastoiditis hospitalized at our tertiary-care center between 2001 and 2016 was conducted. Bacteriology, methods of treatment, hospital course, complications, and otologic history were analyzed. Based on our experience and literature data, a protocol was established in order to standardize management of pediatric acute mastoiditis. Results: All the patients treated for acute mastoiditis were submitted to an intravenous antibiotic regimen. In the analyzed group pharmacological treatment only was applied in 11% of children, in 12% myringotomy/tympanostomy was added, and in the vast majority of patients (77%) mastoidectomy was performed. In our study recurrent mastoiditis was noted in 8% of the patients. We also experienced acute mastoiditis in a cochlear implant child, and in this case, a minimal surgical procedure, in order to protect the device, was recommended. Conclusions: The main points of the management protocol are: initiate a broad-spectrum intravenous antibiotic treatment; mastoidectomy should be performed if the infection fails to be controlled after 48 h of administering intravenous antibiotic therapy. We believe that early mastoidectomy prevents serious complications, and our initial observation is that by performing broad mastoidectomy with posterior attic and facial recess exposure, recurrence of acute mastoiditis can be prevented.

Resumo Introdução: A mastoidite aguda continua a ser a complicação mais comum da otite média aguda. Pode ocorrer também, embora raramente, em pacientes com implante coclear. Entretanto, as recomendações de tratamento para essa doença não são bem definidas ou usadas e, na literatura corrente, as diferenças em relação ao diagnóstico e ao manejo são relativamente significativas. Objetivo: O objetivo deste estudo foi determinar um procedimento padrão e seguro a ser aplicado em caso de mastoidite aguda pediátrica. Método: Foi realizada uma revisão retrospectiva de prontuários de 73 pacientes com 83 episó-dios de mastoidite aguda hospitalizados em nosso centro terciário entre os anos de 2001 a 2016. Foram analisados a bacteriologia, métodos de tratamento, evolução hospitalar, complicações e histórico otológico. Com base em nossa experiência e dados da literatura, foi estabelecido um protocolo para padronizar o tratamento da mastoidite aguda pediátrica. Resultados: Todos os pacientes tratados para mastoidite aguda foram submetidos a antibioticoterapia endovenosa. No grupo analisado, o tratamento farmacológico só foi aplicado em 11% das crianças, em 12% a miringotomia/timpanostomia foi adicionada e na maior parte dos pacientes (77%) foi feita a mastoidectomia. Em nosso estudo, mastoidite recorrente foi observada em 8% dos pacientes. Também observamos mastoidite aguda em criança usuária de implante coclear e, nesse caso, foi recomendada a minimização de procedimentos cirúrgicos, a fim de proteger o dispositivo. Conclusões: Os principais pontos do protocolo de conduta são: iniciar um tratamento antibiótico endovenoso de amplo espectro; a mastoidectomia deve ser feita caso a infecção não seja controlada após 48 horas da administração de antibioticoterapia intravenosa. Acreditamos que a mastoidectomia precoce previne complicações graves e nossa observação inicial é que, com uma mastoidectomia ampla com exposição do ático posterior e do recesso facial, a recorrência de mastoidite aguda pode ser evitada.

Therapeutic approach to pediatric acute mastoiditis - an update.

INTRODUCTION: Acute mastoiditis remains the most common complication of acute otitis media. It may rarely appear also in cochlear implant patients. However, the treatment recommendations for this disease are not precisely defined or employed, and in the current literature the differences regarding both the diagnosis and management are relatively substantial. OBJECTIVE: The aim of this study was to determine a standard and safe procedure to be applied in case of pediatric acute mastoiditis. METHODS: A retrospective chart review of 73 patients with 83 episodes of acute mastoiditis hospitalized at our tertiary-care center between 2001 and 2016 was conducted. Bacteriology, methods of treatment, hospital course, complications, and otologic history were analyzed. Based on our experience and literature data, a protocol was established in order to standardize management of pediatric acute mastoiditis. RESULTS: All the patients treated for acute mastoiditis were submitted to an intravenous antibiotic regimen. In the analyzed group pharmacological treatment only was applied in 11% of children, in 12% myringotomy/tympanostomy was added, and in the vast majority of patients (77%) mastoidectomy was performed. In our study recurrent mastoiditis was noted in 8% of the patients. We also experienced acute mastoiditis in a cochlear implant child, and in this case, a minimal surgical procedure, in order to protect the device, was recommended. CONCLUSIONS: The main points of the management protocol are: initiate a broad-spectrum intravenous antibiotic treatment; mastoidectomy should be performed if the infection fails to be controlled after 48h of administering intravenous antibiotic therapy. We believe that early mastoidectomy prevents serious complications, and our initial observation is that by performing broad mastoidectomy with posterior attic and facial recess exposure, recurrence of acute mastoiditis can be prevented.

Diagnosis and management of pediatric cervical vagal schwannoma.

Schwannomas arising from the vagus nerve are extremely rare in children, with only 15 cases reported in the world literature. We describe a pediatric case of cervical vagal nerve schwannoma successfully treated with cranial nerve-sparing surgery. Our patient presented extensive mass in the right side of the neck with ipsilateral Horner's syndrome. Her first sign, anisocoria, was diagnosed at the age of 1.5 y, making her the youngest vagal schwannoma case ever reported. Using an ultrasonic surgical aspirator and nerve monitoring, a multidisciplinary team successfully removed the mass with no recurrence after 2 years of follow-up.

Different clinical presentation and management of temporal bone fibrous dysplasia in children.

BACKGROUND: Fibrous dysplasia is a slowly progressive benign fibro-osseous disorder that involves one or multiple bones with a unilateral distribution in most cases. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. Temporal bone involvement is the least frequently reported type, especially in children. We reviewed available articles regarding fibrous dysplasia with temporal bone involvement in children and added four patients aged 7 to 17 years who were diagnosed and treated in our institution from 2006 to 2017. The patients' clinical picture comprised head deformity, external canal stenosis, headache, progressive conductive and/or sensorineural hearing loss, tinnitus, and sudden deafness. Two patients had experienced severe episodic vertigo with nausea and vomiting. Two were referred to us with external canal obstruction and secondary cholesteatoma formation with broad middle ear destruction. One was diagnosed with acute mastoiditis and intracranial complications. Optimal management of fibrous dysplasia is unclear and can be challenging, especially in children. In our two patients with disease expansion and involvement of important structures, surgical treatment was abandoned and a "wait-and-scan" policy was applied. The other two were qualified for surgical treatment. One patient underwent two surgeries: modified lateral petrosectomy (canal left open) with pathological tissue removal, cavity obliteration, and subsequent tympanoplasty. Another patient with extensive destruction of the left temporal bone underwent canal wall down mastoidectomy with perisinus abscess drainage and revision 12 months later. Tympanoplasty was unsatisfactory in both patients because of slow progression of the middle ear pathology. None of our patients underwent pharmacological treatment. CONCLUSIONS: In younger patients, observation and a "wait-and-scan" protocol is relevant until significant function, or cosmetic deficits are obvious. Surgery is not preferred and should be delayed until puberty because fibrous dysplasia has a tendency to stabilize after adolescence. In patients with severe symptoms medical treatment can be implemented, but safety of this treatment in children remain controversial.

Combination of Neuroendoscopic and Stereotactic Procedures for Total Resection of Colloid Cysts with Favorable Neurological and Cognitive Outcomes.

BACKGROUND: Despite a wide range of surgical procedures, an unresolved debate remains regarding which attempt is optimal for the treatment of colloid cysts in the third ventricle. In this article, we present a new combination of stereotactic and endoscopic techniques. METHODS: This prospective study includes 27 consecutive patients with symptomatic primary and recurrent colloid cysts. All cysts were removed via a neuroendoscope through a rostral transfrontal, transforaminal approach. The endoscope was supported by an additional cannula fixed in the stereotactic frame. Both tools were inserted into one lateral ventricle through two separate burr holes using stereotactic guidance. RESULTS: The median operating time was 135 minutes. All cysts were removed completely, and no mortality or permanent complications related to surgery occurred. The mean time of observation was 43.5 months (range, 3-78 months), and no clinical or radiologic recurrences were observed. One patient with a history of an infected ventriculoperitoneal shunt did not improve after cyst removal, but improved after subsequent reimplantation of the shunt. In all other cases, symptoms resolved (67%) or decreased (30%). Cognitive functions improved or remained unchanged in all 10 elective cases examined neuropsychologically before and after surgery. CONCLUSIONS: The techniques we describe for removal of colloid cysts are safe and effective, even for recurrent cases, and they provide 100% total resection, favorable cognitive outcomes, low risk of recurrence, and low risk of morbidity. The disadvantages of this method are a longer time for surgery and the need for more complex instrumentation compared with conventional endoscopic resection.

Clipping versus coiling for intracranial aneurysms.

BACKGROUND AND PURPOSE: The aim of this study was to compare results of clipping and coiling for aneurysms of the anterior circle of Willis. Previous studies have not identified a clear superiority of one method over the other. MATERIAL AND METHODS: The study group included 165 consecutive patients. The assessment took into account the risk of death, neurological status according to the scale of the GOS and mRS, the incidence of early complications and quality of life measured by own surveys and questionnaire EORTC QLQ-C30 v. 3.0. RESULTS: Mean follow-up was more than four years. Early and late results of treatment after embolization and clipping for all patients did not differ. Evaluation of patients with bleeding aneurysms demonstrated better outcomes after embolization, however statistical significance was observed only in terms of symptomatic scale score of QLQ-C30 questionnaire (p=0.02). For patients with non-bleeding aneurysms better outcomes were obtained after clipping, but statistical significance was found only in the early results: more excellent results in GOS score at discharge (p<0.03) and fewer complications during hospitalization (p=0.02). CONCLUSIONS: Results of treatment after clipping and coiling do not differ in total for all patients, but differ depending on the presence of bleeding. Patients with bleeding aneurysms achieve better outcomes after coiling, and patients with non-bleeding aneurysms achieve better outcomes after clipping.

Application of intraoperative computed tomography in a neurosurgical operating theatre.

BACKGROUND AND PURPOSE: The authors describe their own experience in use of intraoperative computed tomography (CT) with the Siemens SOMATOM Sensation in 125 cases. MATERIAL AND METHODS: Intraoperative CT of the head was most often used in functional neurosurgery for stereotactic planning in 32 cases and for control of deep brain stimulation electrode placement in 18 cases. In spine surgery, CT was used most often in spine stabilization to control the placement of implants. RESULTS: The implant had to be corrected in 7 cases (17% of 41 procedures), and in those cases the need for a revision procedure was therefore avoided. Intraoperative CT was also widely used in emergency procedures and perioperative complications in 13 cases, for control of intraventricular catheter or Rickham port placement in 8 cases, for evaluation of extent of tumour resection in 4 cases, for verification of electrode placement during percutaneous trigeminal rhizotomy in 3 cases, for evaluation of decompression after cervical corpectomy and thoracic discopathy in 3 cases, in complex fractures in 2 cases and as angio-CT after aneurysm clipping in 1 case. There was no significant prolongation of procedure duration. Intraoperative CT proved to be safe for a patient and for personnel. During the three-year evaluation period, the increasing use and indications for intraoperative CT were noted. Integration of CT with navigation is planned in the near future. CONCLUSIONS: Intraoperative CT is a very useful tool in spine surgery as well as in functional neurosurgery and neurooncology.

Results of neuromodulation for the management of chronic pain.

Background and purpose : Neuromodulative treatment of chronic pain syndromes is a modern mode of treatment of neuropathic and ischaemic pain. Its effectiveness is well documented in the literature. The objective of this work is to present the results of treatment of chronic pain syndromes on the basis of eight-year experience in our department. Material and methods : Since 2002, we have conducted 9 operations of motor cortex stimulation (MCS), 2 of deep brain stimulation (DBS), 45 of spinal cord stimulation (SCS) and 5 of sacral root stimulation (SRS) in the treatment of chronic pain. Results : We obtained good long-term results of neuromodulation in the form of clinical improvement (> 50%) in 4 of 9 patients with MCS (44%), in 13 diagnosed with failed back surgery syndrome (FBSS), 8 with other neuropathic pain, and 11 with angina pectoris from a group of 45 treated with SCS. Sacral root stimulation has been successful in 3 of 5 patients with perianal pain. The best treatment results in SCS, although not statistically significant, were observed in patients treated due to FBSS (13 out of 15) and angina pectoris (11 out of 15) (p = 0.12). In patients with neuropathic pain, peripheral and central, improvement was obtained in 8 out of 15 patients. Conclusions : A good indication for spinal cord stimulation is FBSS and angina pectoris. Motor cortex stimulation is helpful in the treatment of chronic central neuropathic pain. Further observations and a larger group of patients are necessary for a reliable assessment of the effectiveness of neuromodulative treatment of chronic pain in our clinic.

[Intralipid for treatment of local anaesthetic-induced toxicity]. / Intralipid w leczeniu objawów przedawkowania srodków znieczulenia miejscowego.

Regional anaesthesia can be associated with severe complications, which may be due to overdose or accidental intravascular injection of local anaesthetics. The clinical picture varies and depends on the pharmacodynamics of specific drugs, the total dose used, and the route of injection. Among the most common side effects are: excitation, seizures, loss of consciousness, cardiac dysrhythmias, severe shock and cardiac arrest. Cardiovascular resuscitation in such cases may be prolonged and very difficult, mostly because local anaesthetics are lipid soluble and require a long time for redistribution. The majority of cases with lidocaine-induced cardiovascular complications can be successfully resuscitated due to the relatively short duration of action of the drug. Bupivacaine-induced cardiac arrest is probably the most dangerous, with resuscitations in such cases being usually very long and frequently unsuccessful. Recently, intravenous fat emulsion (Intralipid) has been used during resuscitation. This review focuses on the role of intravenous fat emulsions in the treatment of toxicity due to local anaesthetics. The possible antidotal mechanisms are discussed.