"Stent-within-a-Stent" technique for the endovascular treatment of giant aneurysm of basilar artery bifurcation: A case report.

Stents have become very important devices in the treatment of intracranial aneurysms. Flow diverters as high metal coverage stents are developed for hemodynamic treatment of challenging intracranial aneurysms. High level of metal coverage can also be achieved by implementing regular stents telescopically one in another. We present the case of a patient successfully treated for giant aneurysm of basilar artery bifurcation by a "Stent-within-a-Stent" technique. After stent implantation, coil embolization was performed using multiple-sized platinum helical coils. Control angiography performed at the end of the procedure revealed aneurysm occlusion. After 3 years, the patient is fully neurologically recovered, without pyramidal deficit, independently active and able to work.

Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors.

Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an "in-house" gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.

A potential role of mechano-gated potassium channels in meningioma-related seizures.

Every third patient with intracranial meningioma develops seizures of poorly understood etiology. Tumor and peritumoral edema may exert mechanical pressure on the cortex that may affect mechano-gated potassium channels - KCNK2 and KCNK4. These channels regulate neuron excitability and have been related to seizures in some other conditions. The objective of the present study was to explore a potential relation between the levels of these proteins in tumor tissue and adjacent cortex and seizures development. The study included 19 meningioma patients that presented one or more preoperative seizures and 24 patients with no seizures. Tissue samples were collected in the course of surgical removal of the meningioma. Postoperative seizure freedom was achieved in 11 out of 19 patients. The relative level of KCNK2 in the cortical tissue was lower in patients with preoperative seizures. On the other hand, cortical tissue level of KCNK4 was higher in patients that became seizure-free after the surgery. In addition, relative levels of KCNK4 in the cortical and tumor tissue appear to be lowered by the treatment with anti-seizure medication levetiracetam. These results imply that KCNK2 and KCNK4 may be involved in the development of meningioma-related seizures and may represent promising therapeutic targets.

Reconstruction of Moderately and Severely Atrophic Scalp-A Multicentric Experience in Surgical Treatment of Patients Irradiated for Tinea Capitis in Childhood and Surgical Algorithm.

Background and Objectives: Before the introduction of griseofluvin, the use of X-ray radiation was the treatment of choice for tinea capitis. More than half a century later various types of tumors have been found to be associated with childhood irradiation due to tinea capitis, most commonly cancers of the head and neck, as well as brain tumors. The often unusually aggressive and recurrent nature of these tumors necessitates the need for repeated surgeries, while the atrophic skin with an impaired vascular supply due to radiation often poses an additional challenge for defect reconstruction. We present our experience in the surgical treatment of such patients. Materials and Methods: This is a retrospective cohort study. In this study, 37 patients treated for acquired defects of the scalp with a history of irradiation therapy due to tinea capitis in childhood were included in this study, 24 male and 13 female patients. The mean age at the first appointment was 60.6 ± 7.8, with the youngest included patient being 46 and the oldest being 75 years old. Patients' characteristics, surgical treatment, and complications were analyzed and a reconstructive algorithm was developed. Results: Local flaps were used for reconstruction in 34 patients, direct sutures were used in 10 patients and 20 patients received split-thickness skin grafts for coverage of both primary and secondary defects for reconstruction of flap donor sites. One regional flap and one dermal substitute covered by an autologous skin graft were also used for reconstruction. Complications occurred in 43.2% of patients and were significantly associated with the presence of comorbidities (p = 0.001), aseptic bone necrosis (p = 0.001), as well as skin atrophy in frontal, occipital, and parietal region (p = 0.001, p = 0.042 and p = 0.001, respectively). A significant correlation between major complications and moderate skin atrophy was found only in the parietal region (p = 0.026). Conclusions: Unfortunately, many protocols developed for scalp reconstruction are not applicable in the setting of severe or diffuse scalp skin atrophy associated with high tumor recurrence rate and radiation-induced vascular impairment, such as in tinea capitis patients in Serbia. An algorithm has been developed based on the authors' experience in managing these patients.

Proapoptotic and proautophagy effect of H1-receptor antagonist desloratadine in human glioblastoma cell lines.

Glioblastomas are aggressive and usually incurable high-grade gliomas without adequate treatment. In this study, we aimed to investigate the potential of desloratadine to induce apoptosis/autophagy as genetically regulated processes that can seal cancer cell fates. All experiments were performed on U251 human glioblastoma cell line and primary human glioblastoma cell culture. Cytotoxic effect of desloratadine was investigated using MTT and CV assays, while oxidative stress, apoptosis, and autophagy were detected by flow cytometry and immunoblot. Desloratadine treatment decreased cell viability of U251 human glioblastoma cell line and primary human glioblastoma cell culture (IC50 value 50 µM) by an increase of intracellular reactive oxygen species and caspase activity. Also, desloratadine decreased the expression of main autophagy repressor mTOR and its upstream activator Akt and increased the expression of AMPK. Desloratadine exerted dual cytotoxic effect inducing both apoptosis- and mTOR/AMPK-dependent cytotoxic autophagy in glioblastoma cells and primary glioblastoma cell culture.

A unique case of intracranial collision tumor composed of ganglioglioma WHO gr I and supratentorial ependymoma WHO gr III: case-based literature review.

PURPOSE: Intracranial collision tumor is a rare entity that represents the coexistence of two histopathological different tumor types in the same area without histological admixture or an intermediate cell population zone. So far, several cases of collision tumors with ganglioglioma as its component have been reported in the literature, while supratentorial ependymoma has never been reported as a collision tumor component. We are presenting a unique case of collision tumor in patient without previous history of head trauma, neurological surgery, radiotherapy, or phakomatosis. METHODS AND RESULTS: A 17-year-old male with no previous history of head trauma, neurological surgery, radiotherapy, or phakomatosis was presented to our clinic with grand mal seizure. Brain magnetic resonance imaging with gadolinium contrast was done revealing a contrast-enhancing lesion of right frontal lobe closely related to dura, surrounded by perifocal edema. The patient underwent a gross total tumor resection. Histological examination revealed collision tumor with two distinct components: ganglioglioma and supratentorial ependymoma. CONCLUSION: To our best knowledge, no previous reports of collision tumor composed of ganglioglioma and supratentorial ependymoma in a single patient have been reported. We believe that this report could significantly contribute to further surgical practice as well as to treatment decision for these types of collision tumors.

Total diagnostic interval in children with brain tumours in a middle-income country: national experience from Serbia.

PURPOSE: The aim was to evaluate the total diagnostic interval (TDI) and presenting complaints in children with brain tumours in Serbia. METHODS: This study retrospectively analysed 212 children aged 0-18 years newly diagnosed with brain tumours in two tertiary centres from mid-March 2015 to mid-March 2020 covering virtually all children with brain tumours in Serbia. TDI was calculated as the difference between the date of diagnosis and the date of symptom onset presented as a median in weeks. This variable has been evaluable for 184 patients. RESULTS: Overall TDI was 6 weeks. TDI was significantly longer in patients with low-grade tumours (11 weeks) than in patients with high-grade tumours (4 weeks). Children with the most frequent complaints (headache, nausea/vomiting and gait disturbance) were more likely to be diagnosed sooner. Patients with a single complaint had significantly longer TDI (12.5 weeks) contrasted to patients with multiple complaints (5 weeks). CONCLUSION: TDI with a median of 6 weeks is similar to other developed countries. Our study supports the view that low-grade tumours will present later than high-grade tumours. Children with the commonest complaints and children with multiple complaints were more likely to be diagnosed sooner.

Factors associated with preoperative and early and late postoperative seizures in patients with supratentorial meningiomas.

OBJECTIVE: Risk factors for epilepsy in meningioma patients are not yet clearly defined, however, seizure freedom is a significant factor for quality of life after surgery. METHODS: We performed a retrospective study of the 333 adult patients who received surgery for supratentorial meningioma at our center. Various clinical, radiological, and surgical variables were included in the multivariate regression, and the outcomes measured were the occurrence of seizure(s) preoperatively, during the hospitalization, and during the follow-up period. RESULTS: A total of 89 (26.7%) patients experienced preoperative seizures, of whom 62.9% were seizure free after the surgery. Of 244 patients without epilepsy before surgery, 11.9% had at least one seizure postoperatively. In total, 63 of our patients (18.9%) experienced seizures after the surgery, of whom 20 had refractory epilepsy. Multivariate analysis identified the following predictors of preoperative seizures: the absence of headache (OR: 0.23, CI: 2.55-8.50), the presence of significant peritumoral edema (OR: 4.35, CI: 2.57-7.35), and younger age (OR: 0.97 per year increase, CI: 0.95-0.99). Factors associated with early postoperative seizures were: younger age (OR: 0.96 per year increase, CI: 0.93-0.99) and the presence of preoperative seizures (OR: 2.73, CI: 1.13-6.57), while the presence of preoperative seizures (OR: 4.73, CI: 2.05-10.92), tumor progression (OR: 5.38, CI: 2.25-12.89), and neurological worsening (OR: 5.21 CI: 1.72-15.81) were significant for late postoperative seizures. SIGNIFICANCE: Our results from a single-center meningioma cohort confirm, in general, data from some previous studies regarding patients' characteristics for both preoperative and overall postoperative epilepsy. Besides previously described risk factors, younger age was important for preoperative and early postoperative seizures. Epilepsy is common in patients with recurrence of meningioma, but the variables of significance for refractory seizures in these patients require further examination.

Clinical Profile and Outcome of 806 Pediatric Oncology Patients Treated With Radiotherapy at the Serbian National Cancer Center.

Radiotherapy plays an important role in the multimodal treatment of childhood cancer. Our objective was to provide an analysis of pediatric oncology patients treated with radiotherapy in a national referral institution in Serbia. A retrospective chart review of children treated with radiotherapy between January 2007 and July 2018 was conducted. Of the 806 patients who were identified, 767 formed the basis of this study. CNS tumors (31.2%) were the most common tumors followed by leukemias (17.3%) and bone tumors (14.3%). The most common indication for radiotherapy was in adjuvant setting (69.1%). Anesthesia or sedation was performed on 115 patients. The 5-year and 10-year overall survival rates were 65.7% and 62.1%, respectively. A significant difference in survival in relation to tumor type was seen. The best survival rates were obtained in patients with retinoblastoma, followed by lymphomas and nephroblastoma, while patients with bone sarcomas had the worst survival. The intent of radiotherapy treatment was also a parameter associated with survival. Patients treated with palliative and definitive intent lived shorter than patients treated with prophylactic and adjuvant intent. Our study showed that good treatment outcomes can be achieved in specialized centers with an experienced team of professionals who are dedicated to pediatric oncology.

Case Report: Atypical Solitary Brain Metastasis: The Role of MR Spectroscopy In Differential Diagnosis.

Background: Metastatic brain tumors are typically located at the cerebral hemispheres or the cerebellum and most frequently originate from primary breast or lung tumors. Metastatic lesions are usually associated with blood-brain barrier disruption, solid or ring-like contrast enhancement, and perilesional vasogenic edema on brain imaging. Even in cases where metastases are predominantly cystic, enhancement of the minor solid component can be detected. In contrast, non-enhancing secondary brain tumors were only reported in a patient after antiangiogenic treatment with bevacizumab. Case report: We report a case of a 54-year-old male who presented with left-sided weakness and multiple seizures. Brain magnetic resonance imaging revealed a T2-weighted heterogeneous solid tumor in the right frontoparietal parasagittal region, with no apparent enhancement on T1-weighted post-contrast images and no evident perilesional edema. Further MRS analysis revealed markedly increased choline and lipid peaks. The patient underwent craniotomy for tumor removal. Histopathology revealed findings consistent with metastatic non-microcellular neuroendocrine lung cancer. positron emission tomography/computed tomography (PET/CT) revealed a stellate lesion within the right upper lung lobe, compatible with primary lung cancer. Conclusion: Non-enhancing brain metastatic tumors are rarely reported in the literature, usually following antiangiogenic treatment. Here, we report the first ever case of a non-enhancing metastatic brain tumor with no prior history of antiangiogenic treatment, with particular emphasis on the importance of MRS analysis in atypical brain lesions.

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide.

A personalized approach to chemoradiation is important in reducing its potential side effects and identifying a group of patients prone to toxicity. MicroRNAs have been shown to have a predictive potential for radiotoxicity. The goal of the study was to test if levels of miRNA in peripheral blood mononuclear cells of glioblastoma patients are associated with toxicity and to identify the peak time point for toxicity. MicroRNA-10b/21/34a levels were measured in 43 patients with and without toxicity, at baseline, at the 15th, and at the 30th fraction by Real-Time quantitative Polymerase Chain Reaction. MicroRNA-10b/21 levels increased with toxicity grade (p = 0.014; p = 0.013); miR-21/34a levels were significantly different between patients with and without toxicity at the 15th fraction (p = 0.030; p = 0.045), while miR-34a levels significantly changed during treatment (p < 0.001). All three miRNAs showed a significantly high positive correlation with one another. MiR-34a might be considered as a predictive factor for toxicity due to its changes during treatment, and differences between the groups with and without toxicity; miR-10b might be used to predict toxicity; miR-10b/21 might be used for predicting the grade of toxicity in GB patients.

The sellar region as presenting theater for hematologic malignancies-A 17-year single-center experience.

Hematological neoplastic mass lesions of the sellar region are rare. We identified five cases of hematological malignancy with first presentation in the sellar region from our departmental database of 1,405 patients (0.36%) with sellar lesions diagnosed over the 17-year period (2005-2021). All patients were females (mean age 55.2 ± 3.4 years). One patient had multiple myeloma (MM), one patient had acute myeloid leukemia (AML), while three other patients had lymphoma (intravascular lymphoma (IVL, n = 1) or non-Hodgkin's lymphoma (NHL, n = 2). Most patients presented with ophthalmoplegia, and one patient with diabetes insipidus (DI), with short duration of symptoms (median 30 days). All patients had an elevated erythrocyte sedimentation rate and altered blood count, while patients with lymphoma had elevated lactate dehydrogenase (LDH). Sellar mass was demonstrated in three patients while the patient with IVL had an empty sella and in the AML patient posterior lobe T1W hyperintensity was lost. Two patients (IVL and NHL) presented with multiple anterior pituitary deficiencies and one patient (AML) had DI. All patients were treated with chemotherapy. Two patients responded well to treatment (one had reversed hypopituitarism), while three patients died. Differential diagnosis of sellar-parasellar pathology should include suspicion of hematological malignancy, particularly in patients with short duration of nonspecific symptoms, neurological signs (ophthalmoplegia), blood count alterations and LDH elevation, pituitary dysfunction and imaging features atypical for pituitary adenoma. Early diagnosis is crucial for timely initiation of hematological treatment aimed at inducing disease remission and partial or full recovery of pituitary function.

Clinical profile, treatment and outcome of pediatric brain tumors in Serbia in a 10-year period: A national referral institution experience.

OBJECTIVE: This study aimed to evaluate the characteristics of children with primary brain tumors, the effectiveness of treatment modalities, and to detect factors related to the outcome. METHODS: A detailed analysis was performed on a series of 173 pediatric patients treated in a Serbian referral oncology institution between 2007 and 2016, based on their clinical, histological, treatment, and follow-up data. RESULTS: Mean survival time of all children was 94.5months. 2-, 5- and 10-year overall survival probabilities were 68.8%, 59.4%, and 52.8%, respectively. Patients with supratentorial tumors had longer survival than patients with infratentorial tumors and patients with tumors in both compartments (p = 0.011). Children with the unknown histopathology (brainstem glioma) and high-grade glioma had a shorter life than embryonal tumors, ependymoma, and low-grade glioma (p<0.001). Survival of the children who underwent gross total resection was longer than the children in whom lesser degrees of resection were achieved (p = 0.015). The extent of the disease is a very important parameter found to be associated with survival. Patients with no evidence of disease after surgery had a mean survival of 123 months, compared with 82 months in patients with local residual disease and 55 months in patients with disseminated disease (p<0.001). By the univariate analysis, factors predicting poor outcome in our series were the presentation of disease with hormonal abnormalities, tumor location, and the extent of the disease, while the factors predicting a better outcome were age at the time of diagnosis, presentation of the disease with neurological deficit, and type of resection. By the multivariate analysis, the extent of the disease remained as the only strong adverse risk factor for survival (HR 2.06; 95% CI = 1.38-3.07; p<0.001). CONCLUSIONS: With an organized and dedicated multidisciplinary team, the adequate outcomes can be achieved in a middle-income country setting. The presence of local residual disease after surgery and disseminated disease has a strong negative effect on survival.

Mapping the journey of transition: a single-center study of 170 childhood-onset GH deficiency patients.

OBJECTIVE: To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP). DESIGN: Single- center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16-25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP. RESULTS: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%). CONCLUSION: The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD.

Long-lasting Thrombocytopenia after Transient Pancytopenia Induced by Short-Term Concomitant Radiotherapy and Temozolomide.

We describe long-lasting and incompletely resolved thrombocytopenia after transient profound pancytopenia in a 62-year-old female patient with glioblastoma after short-term radiotherapy with temozolomide. Pancytopenia was present for more than 4 weeks and thrombocytopenia for more than 6 months, without platelet recovery to normal levels. LEARNING POINTS: Some patients may experience severe haematological manifestations after even short-term radiotherapy with temozolomide.In everyday practice, clinical models precisely predicting the haematological toxicity of concomitant treatment with temozolomide and radiotherapy is necessary, especially in countries where genetic tests are not available.Incomplete recovery of the cells of a particular bloodline over a long period may necessitate permanent discontinuation of chemotherapy or radiotherapy.

Low-grade epilepsy-associated tumour management with or without presurgical evaluation: a multicentre, retrospective, observational study of postsurgical epilepsy outcome.

Low-grade epilepsy-associated neuroepithelial tumours (LEATs) encompass the broad spectrum of tumours associated with epilepsy. Since the postsurgical seizure outcome in LEATs is favourable, it is speculated that epileptological presurgical evaluation (EPE) might not be required for patients with LEATs. A multicentre study involving referring epilepsy and neurosurgery centres was performed, aimed at evaluating postsurgical epilepsy outcome in patients with LEATs, with and without EPE, including long-term video-EEG monitoring (vEEGM). In total, 149 surgically treated patients were enrolled (age: 31±14 years; age at surgery: 26.4±13.1 years; males; 55.7%) with histopathological confirmation of LEATs and follow-up of more than six months. All patients had undergone standard assessment: clinical, routine EEG and brain MRI. In addition to vEEGM, EPE included other additional investigations. Epileptologists did not assess patients treated in neurosurgical centres. The EPE was performed in 51% of patients. Histopathological diagnosis revealed ganglioglioma in 43.6%, DNET in 32.9%, pilocytic astrocytoma in 17.4%, and others in 6.1% of patients. The majority of patients were seizure-free (ILAE epilepsy surgery outcome Class 1; 71.1%). The median follow-up period was 36 months. Patients who were rendered seizure-free were younger (mean age: 24.2±12.2) than those who were not seizure-free (31.8±14.0) (p=0.001). No difference was identified between evaluated and non-evaluated patients with respect to seizure freedom (p=0.45). EPE patients had a longer epilepsy duration (median: 10 years) and a higher proportion of drug resistance (73.6%) compared to non-evaluated patients (median: two years; 26.4%) (p<0.001). Based on a significant difference in major clinical variables, that may well affect postoperative results, the similar postsurgical seizure outcome in groups with and without EPE observed in our study should be considered with caution, and conclusions as to whether there is value in formal presurgical evaluation in LEAT patients cannot be drawn. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences.

The Impact of Intraoperative Monitoring on Extent of Resection and Long-Term Neurological Outcomes: A Series of 39 Intramedullary Ependimomas.

AIM: To analyze the impact of intraoperative neurophysiological monitoring (IONM) on the extent of removal and long-term neurological outcomes in a series of grade II ependymomas. MATERIAL AND METHODS: We retrospectively reviewed 88 consecutive patients who underwent surgical resection of an intramedullary spinal cord tumor (IMSCT) at the Clinic of Neurosurgery of the Clinical Center of Serbia in Belgrade between January 2012 and December 2017. In all, 39 patients (25 males and 14 females; mean age 46.16 years) with grade II ependymomas were enrolled in this study; the mean follow-up time was 49.84 months. The modified McCormick Scale (mMCS) was used to assess the short- and long-term outcomes, and the patients were divided into two groups based on whether they underwent IONM. RESULTS: The gross-total removal rate was 89.7%, and it was not influenced by use of IONM, location or tumor size. Upon admission,43.2% of the patients were dependent (grades IV and V), while 56.8% were independent (grades I, II and III), according to the mMCS. After 3 months of follow-up, 76.9% of the patients maintained or improved their neurological status, but this percentage was reduced after long-term follow-up. CONCLUSION: Total surgical resection with good neurological outcomes can be achieved in the vast majority of patients with grade II ependymomas; it is important to emphasize that the use of IONM allows acceptable extent of resection and provides better results in terms of functional outcomes, with lower morbidity rates. Therefore, no correlation was demonstrated between the decrease in the basal amplitudes of IONM and D-waves and poor neurological outcomes.

Predictors of unfavourable outcome in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Mortality rates following aneurysmal subarachnoid haemorrhage (aSAH) have decreased due to improvements in diagnoses and the management of complications, as well as early obliteration of the aneurysms. Neurogenic pulmonary oedema (NPO) is a clinical syndrome associated with an acute increase in intracranial pressure and a release of catecholamines into the circulation. This study investigated independent predictors of unfavourable outcomes (Glasgow Outcome Scores 1, 2 or 3) in patients with aSAH. MATERIALS AND METHODS: A total of 262 patients with aSAH (162 females) were included in this prospective study. Clinical characteristics were assessed, and electrocardiographic, serum cardiac and inflammatory biomarker measurements were recorded on admission. Outcomes were assessed three months after admission. Univariate and multivariate analyses of these data were used to predict unfavourable outcomes. RESULTS: A total of 156 patients (59.54%) had unfavourable outcomes. Compared to those who had favourable outcomes, patients with unfavourable outcomes were significantly older (54.37 ± 10.56 vs. 49.13 ± 10.77 years; p < 0.001) and had more severe aSAHs (Hunt and Hess grades ≥ 3: 82.7% vs. 39.6%; p < 0.001). Patients with unfavourable outcomes were more likely to have NPO (10.3% vs. 2.8%; p = 0.023), hydrocephalus (34.0% vs. 20.8%; p = 0.02), and aneurysm reruptures (28.2% vs. 3.8%; p < 0.001). Independent predictors of an unfavourable outcome included Hunt and Hess grades ≥ 3 (odds ratio [OR], 4.291; 95% confidence interval [CI], 2.168-8.491; p < 0.001), increased systolic blood pressure on admission (OR, 1.020; 95% CI, 1.002-1.038; p = 0.03), increased heart rate (HR) on admission (OR, 1.024; 95% CI, 1.001-1.048; p = 0.04), and aneurysm rerupture (OR, 4.961; 95% CI, 1.461-16.845; p = 0.01). CONCLUSIONS: These findings suggest that aneurysm reruptures, as well as increased blood pressure and HR, are associated with unfavourable outcomes in patients with aSAH.

The human biomonitoring study in Serbia: Background levels for arsenic, cadmium, lead, thorium and uranium in the whole blood of adult Serbian population.

The purpose of this study was to establish reference values (RVs) for the occupationally- and environmentally-important toxic elements in the whole blood of adult Serbian population for the first time. Contaminated drinking water with arsenic, high share of smokers in the country, removing tetraethyl lead from the gasoline and war attack at the end of the twentieth century were some of the reasons to provide background information for arsenic (As), cadmium (Cd), lead (Pb), thorium (Th), and uranium (U) in the blood of the Serbian population. The whole blood samples were collected from the healthy respondents living in the Belgrade and surrounding areas of the capital (n = 305; w/m ratio = 154/151; mean age: 41 ±â€¯2). The concentrations of toxic metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Reference values were estimated as the lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI), together with the selected percentiles (P2.5-P97.5). The obtained geometric mean (GM) for As, Cd, Pb, Th, and U were: 0.50 ng/g, 0.32 ng/g, 20.94 ng/g, 0.30 ng/g, and 0.06 ng/g, respectively. The influences of age, sex and lifestyle on results were considered. Women have significantly higher levels of Cd and Th than men. The increased level of Th was observed in the aged group below 40 years, while smokers had significantly higher levels of Pb and double higher level of Cd in the blood than non-smokers (p < 0.05). In comparison with other population groups worldwide, the Serbian population had significantly higher levels of Th and U (up to 100 times higher). These findings could contribute to better understanding of the molecular basis for the development of various health hazards, including the increased incidence of cancer among the Serbian population which need be confirmed by clinical studies.

Clinical case seminar: Familial intracranial germinoma.

BACKGROUND: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurance. Since ICG invades hypothalamus and/or pituitary, the endocrine dysfunction is one of the common determinants of these tumors. We presented two brothers with the history of ICG. Patient 1 is a 25-year-old male who had been suffering from the weakness of the right half of his body at the age of 18. Cranial MRI revealed mass lesion in the left thalamus. He underwent neurosurgery, tumor was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumor after a radiation therapy. At the age of 22 the diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Patient 2 is a 20-year old boy who was presented with diabetes insipidus at the age of 12. MRI detected tumor in the third ventricle and pineal region. After the endoscopic tumor biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy, and treated with GH during childhood. At the age of 18 GH replacement was reintroduced. A six month follow-up during the next two years in both brothers demonstrated the IGF1 normalization with no MRI signs of tumor recurrence. CONCLUSION: To the best of our knowledge so far, only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside of Japan. They are treated successfully with GH therapy in adult period. < /p > < p >.