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Purpose People with drug-refractory epilepsy are potential candidates for surgery. In many cases, epileptogenic zone localization requires intracranial investigations, e.g., via ElectroCorticoGraphy (ECoG), which uses subdural electrodes to map eloquent areas of large cortical regions. Precise electrodes localization on cortical surface is mandatory to delineate the seizure onset zone. Simple thresholding operations performed on patients’ computed tomography (CT) volumes recognize electrodes but also other metal objects (e.g., wires, stitches), which need to be manually removed. A new automated method based on shape analysis is proposed, which provides substantially improved performances in ECoG electrodes recognition. Methods The proposed method was retrospectively tested on 24 CT volumes of subjects with drug-refractory focal epilepsy, presenting a large number (> 1700) of round platinum electrodes. After CT volume thresholding, six geometric features of voxel clusters (volume, symmetry axes lengths, circularity and cylinder similarity) were used to recognize the actual electrodes among all metal objects via a Gaussian support vector machine (G-SVM). The proposed method was further tested on seven CT volumes from a public repository. Simultaneous recognition of depth and ECoG electrodes was also investigated on three additional CT volumes, containing penetrating depth electrodes. Results The G-SVM provided a 99.74% mean classification accuracy across all 24 single-patient datasets, as well as on the combined dataset. High accuracies were obtained also on the CT volumes from public repository (98.27% across all patients, 99.68% on combined dataset). An overall accuracy of 99.34% was achieved for the recognition of depth and ECoG electrodes. Conclusions The proposed method accomplishes automated ECoG electrodes localization with unprecedented accuracy and can be easily implemented into existing software for preoperative analysis process. The preliminary yet surprisingly good results achieved for the simultaneous depth and ECoG electrodes recognition are encouraging. Ethical approval n°NCT04479410 by “IRCCS Neuromed” (Pozzilli, Italy), 30th July 2020.

Background Postoperative spinal epidural hematoma is a rare complication of anterior cervical discectomy and fusion. This condition may rapidly produce severe neurologic deficits, often requiring a prompt surgical decompression. A multilevel extension of the epidural bleeding has been rarely described after anterior cervical procedures. In such cases, the choice of the most suitable surgical approach may be challenging. Herein, we describe an effective surgical decompression of a C2-T1 ventral epidural hematoma following anterior cervical discectomy and fusion at the C5-C6 level. Methods By reopening the previous approach, the C5-C6 intersomatic cage was removed and the surgical field inspected for bleeding. After removal of the spinal epidural hematoma at this level, a lumbar external drainage catheter was inserted into the epidural space to perform multiple irrigations with saline solution until the washing fluid was clear. Results Immediate postoperative cervical computed tomography and magnetic resonance imaging revealed gross total removal of the epidural hematoma and complete decompression of the spinal cord all along the affected tract. Early postoperative neurologic examination revealed mild lower extremity weakness that fully recovered within hours. Conclusions Although rare, multilevel epidural hematoma following anterior cervical decompression represents a serious complication. The revision of the previous anterior cervical approach may be considered the first treatment option, allowing to control the primary bleeding site. Catheter irrigation of the epidural space with saline solution may be a useful technique for removal of unexposed residual blood collection, avoiding the need for posterior laminectomy or other unnecessary bone demolition.

Background. It is unknown how much precociously the cigarette smoking (CS) may compromise the integrity of the cardiovascular (CV) system. Myocardial function can be routinely assessed by conventional echocardiography, but abnormalities are only detected when somewhat a remodelling has already occurred. These limitations could be overcome by strain imaging. Methods. We evaluated whether young smokers with normal left ventricular (LV) geometry, wall motion and ejection fraction may present abnormalities in myocardial deformation, both at rest and during physical effort. We selected 50 young smokers with no additional CV risk factors, and 60 non-smokers to undergo a standardized exercise-test. Consistently, we evaluated the CV adaptation to exercise by both conventional echocardiography and speckle-tracking analysis (2D-STE). Results. We found no difference between smokers and controls regarding baseline characteristics; as expected, smokers presented with lower HDL-cholesterol (p

Background Presacral schwannomas are rare benign tumors that may reach large size before becoming symptomatic. Total surgical removal has been considered the best treatment option. Tumors arising from the presacral area are commonly managed through anterior approaches, whereas posterior approaches are used for pure intrasacral tumors or large lesions with both intrasacral and presacral extension, alone or in combination with anterior approaches. Methods We describe a quick and minimally invasive navigation-guided posterolateral approach to a right presacral L5 schwannoma. The lesion was microsurgically removed through high-speed drilling of the upper portion of the right sacral ala, under intraoperative neurophysiologic monitoring. Results The postoperative course was unremarkable, and the patient experienced improvement in his sensory disturbance. Postoperative magnetic resonance imaging and computed tomography scan showed the complete excision of the lesion and the removal of the upper sacral ala with preservation of the right L5-S1 articular complex. The histologic examination confirmed a schwannoma (World Health Organization grade I). Conclusions The posterolateral transsacral ala approach may represent a minimally invasive option in the surgical management of presacral well-circumscribed benign tumors. Spinal navigation could be properly used to facilitate lesion exposure and to minimize the bone removal. The intraoperative neurophysiologic monitoring is an essential tool for the preservation of the lumbosacral nerve roots.

Background Colloid cysts of the third ventricle are rare benign lesions, which amount to approximately 1% of all intracranial tumors. Because these lesions grow predominantly in the anterior aspect of the third ventricle, they may cause the occlusion of the foramina of Monro, generating obstructive hydrocephalus. Surgery is mandatory in cases of large cysts and/or in symptomatic patients. Among the different surgical strategies described in colloid cysts surgery, the microsurgical transcallosal approach still constitutes the procedure of choice in many centers. In this study, we describe a modified microsurgical transcallosal approach, the interhemispheric transgenual approach, in a series of 13 consecutive patients operated on for colloid cysts of the third ventricle. Methods All the procedures were performed by the senior author (V.E.) at Neuromed Institute of Pozzilli (Is, Italy). The operative procedure is described in its various steps, illustrating the differences and potential advantages compared with the traditional microsurgical transcallosal approach. Results No surgical complications or new-onset neurologic deficits were observed in the postoperative period. The postoperative magnetic resonance imaging confirmed in all cases complete lesion removal without any sign of parenchymal damage. No lesion recurrence or need for permanent cerebrospinal fluid diversion was detected in the patients of this series during the follow-up period. Conclusions In our experience, the interhemispheric transgenual approach has been effective in providing complete colloid cyst removal with minimal risk of vascular and parenchymal damage. Further studies are required to confirm its efficacy in improving the overall outcome of the microsurgical transcallosal approach.

Hydrocephalus (HC) can be associated with vestibular schwannoma (VS) at presentation. Although spontaneous resolution of HC after VS removal is reported, first-line treatment is varied including preoperative ventriculoperitoneal (VP) shunt, external ventricular drainage (EVD), or lumbar drainage (LD). We performed a systematic review to clarify optimal management of HC associated with VS at presentation, as well as characteristics of patients with initial and persistent HC after VS removal, and prevalence of HC associated with VS. Fourteen studies were included. Patients were grouped according to the timing of HC treatment. The overall rate of VP shunts was 19.4%. Among patients who received VS removal as first-line treatment, 6.9% underwent permanent shunts. In a subgroup of 132 patients (studies with no-aggregate data), t test analysis for mean tumor size (P = 0.02) and mean CSF protein level (P

Bitemporal epilepsy (biTLE), a potential cause of failure in TLE surgery, is rarely associated with unilateral HS and could be suggested by not lateralizing ictal scalp EEG/interictal PET-FDG findings. We evaluated the proportion of biTLE in a population of drug-resistant TLE-HS subjects who underwent intracranial investigation for lateralizing purpose.We retrospectively included all consecutive refractory TLE-HS patients and not lateralizing ictal scalp EEG/interictal PET-FDG findings, investigated by intracranial bilateral longitudinal hippocampal electrodes. Demographic characteristics, electroclinical findings and seizure outcome were evaluated.We identified 14 subjects (7 males; mean age 39.5 years; mean age at disease onset 14.4 years), 7 of them had biTLE diagnosed after intracranial investigations. In the remaining 7 with unilateral epileptogenesis (uniTLE) anterior temporal lobectomy was performed (6/7 were in Engel class I). Preoperative neuropsychological assessment differentiated biTLE from uniTLE, as it was normal in six uniTLE patients but only in one with biTLE (p 0.05).Not lateralizing ictal scalp EEG and functional imaging findings in TLEHS should alert about the possibility of a true biTLE also in presence of unilateral findings at MRI. Intracranial investigations with bilateral longitudinal hippocampal electrodes can localize the EZ with a good risk-benefit profile. Consistently with the warning on memory functions in TLE patients explored by using longitudinal hippocampal electrodes, further studies are needed to better define the optimal investigation strategy.

To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3 Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) who underwent surgery.We studied 78 consecutive patients with TLE-HS who underwent surgery and were followed up for at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were subdivided in subgroups according to the presence of TB or TA. Subgroups were compared on demographic, clinical, neuropsychological data and seizure outcome.TB was found in 39 (50%) patients, while TA was found in 32 (41%) patients, always ipsilateral to HS, with a considerable degree of overlap (69%) between TB and TA (p=0.01). Patients with temporopolar abnormalities did not significantly differ from those without TB or TA with regard to sex, age, age of epilepsy onset, duration of epilepsy, history of febrile convulsions or birth complications, side of surgery, seizure frequency at surgery, presence of GTCSs, and, in particular, seizure outcome. On the other hand, TB patients show a less frequent family history of epilepsy (p.05) while age at epilepsy onset showed a trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did not significantly differ from those without TA on any variable, except for age at epilepsy onset, which was significantly lower for the TA group (p.05). History of birth complications and longer duration of epilepsy also showed a trend to be associated with TA (p=.08). Multivariate analysis corroborated the association between temporopolar abnormalities and absence of family history of epilepsy and history of birth complications.High-field 3 T MRI in the preoperative workup for epilepsy surgery confirms that temporopolar abnormalities are frequent findings in TLE-HS patients and may be helpful to lateralize the epileptogenic zone. Their presence did not influence seizure outcome.

Background and aims Young cigarette smokers may already present with early signs of vascular inflammation and damage; biglycan (BGN) has been shown to play a critical role in the initiation and progression of vascular lesions, also in young smokers. We investigated whether after smoke cessation, monocyte BGN expression is reduced; moreover, we evaluated any improvement of pro-atherogenic profile and arterial stiffness (AS), and their relationship with BGN in abstinent smokers. Methods Two-hundred-fifty-one young people who had decided to quit smoking were enrolled; of these, 71 had completed the 12-month observation period maintaining smoking abstinence. At enrollment and 12 months later, we evaluated anthropometrics, laboratory profile, carotid-femoral pulse wave velocity (cf-PWV), carotid intima-media thickness (cIMT), BGN expression. Results After 12-month smoke abstinence, we found a significant decrease in inflammatory markers (Hs-CRP: −23.3%; fibrinogen: −11.8%; IL-6: −9.2%), and increased HDL-C levels (+9.3%); blood pressure values were also slightly reduced. cf-PWV (−8.9%) appeared to be improved; cIMT remained unchanged. BGN expression appeared to be reduced (−42.8% relative reduction). BGN reduction appeared to be associated with fibrinogen reduction, and smoking burden. Reduced cf-PWV appeared to be dependent on change in fibrinogen, SBP, IL-6, and BGN by multiple regression analysis. Conclusions After the first year of smoke abstinence, the levels of IL-6, CRP, fibrinogen, HDL-C, and BGN expression, as well cf-PWV, are significantly improved as compared to baseline. This is the first evidence that removing exposure to a well-known cardiovascular risk factor, such as cigarette smoking, leads to significant reduction of BGN expression.

Drug-induced aseptic meningitis (DIAM) represents a diagnostic challenge since clinical and cerebrospinal fluid (CSF) findings may be indistinguishable from a bacterial meningitis. Intravenous immunoglobulin (IVIg) are commonly used in a variety of diseases, including inflammatory and autoimmune disorders. Although usually well-tolerated, various adverse effects have been reported. DIAM is a serious neurological side effect of IVIg therapy: albeit rare (0.067% of all IVIg infusions), the condition represents an important diagnostic challenge and should be considered by physicians. Here we report a case of an aseptic meningitis induced by IVIg therapy in a child with acute Epstein-Barr virus (EBV) infection and thrombocytopenia.

PurposeTo assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up.MethodsWe studied 60 consecutive patients with TLE–HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome.ResultsTB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p

Purpose The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. Method This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001–2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. Results Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I–II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). Conclusion Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.

Peroxisome proliferator-activated receptor alpha (PPARα) has been involved in the regulation of somatotroph tumour cells and may be targeted by different drugs, some of them are in current clinical use. The aim of this study was to investigate the expression of PPARα in additional phenotypes of pituitary adenomas (PA), the relationship between PPARα and its potential molecular partner aryl hydrocarbon receptor interacting protein (AIP) in these tumours, and the effects of PPARα agonists on lactotroph cells. Seventy-five human PA – 57 non-functioning (NFPA) and 18 prolactinomas (PRL-PA) – were characterised for PPARα and AIP expression by real time RT-PCR and/or immunohistochemistry (IHC), and the effects of fenofibrate and WY 14 643 on MMQ cells were studied in vitro. PPARα was expressed in a majority of PA. PPARα immunostaining was observed in 93.7% PRL-PA vs. 60.6% NFPA (p=0.016), the opposite being found for AIP (83.3% in NFPA vs. 43.7% in PRL-PA, p=0.003). PPARα expression was unrelated to gonadotroph differentiation in NFPA, but positively correlated with tumour volume in PRL-PA. Both drugs significantly reduced MMQ cell growth at high concentrations (100–200 μM). At the same time, despite modest stimulating effects on PRL secretion were observed, these were overcome by the reduction in cell number. In conclusion, PPARα is commonly expressed by PRL-PA and NFPA, regardless of AIP, and may represent a new target of PPARα agonists.

To elucidate the physiologic function of renal globotriaosylceramide (Gb3/CD77), which up-to-date has been associated exclusively with Shiga toxin binding, we have analyzed renal function in Gb3-deficient mice. Gb3 synthase KO (Gb3S−/−) mice displayed an increased renal albumin and low molecular weight protein excretion compared to WT. Gb3 localized at the brush border and within vesicular structures in WT proximal tubules and has now been shown to be closely associated with the receptor complex megalin/cubilin and with albumin uptake. In two clinically relevant mouse models of acute kidney injury caused by myoglobin as seen in rhabdomyolysis and the aminoglycoside gentamicin, Gb3S−/− mice showed a preserved renal function and morphology, compared to WT. Pharmacologic inhibition of glucosylceramide-based glycosphingolipids, including Gb3, in WT mice corroborated the results of genetically Gb3-deficient mice. In conclusion, our data significantly advance the current knowledge on the physiologic and pathophysiologic role of Gb3 in proximal tubules, showing an involvement in the reabsorption of filtered albumin, myoglobin and the aminoglycoside gentamicin.

Objective γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in adult central nervous system, and profound alterations of GABA receptor functions are linked to temporal lobe epilepsy (TLE). Here we describe the functional relationships between GABA receptors type B (GABAB R) and type A (GABAA R) in human temporal cortex and how TLE affects this aspect of GABAergic signaling. Methods Miniature inhibitory postsynaptic currents (mIPSCs) were recorded by patch-clamp techniques from human L5 pyramidal neurons in slices from temporal cortex tissue obtained from surgery. Results We describe a constitutive functional crosstalk between GABAB Rs and GABAA Rs in human temporal layer 5 pyramidal neurons, which is lost in epileptic tissues. The activation of GABAB Rs by baclofen, in addition to the expected reduction of mIPSC frequency, produced, in cortex of nonepileptic patients, the prolongation of mIPSC rise and decay times, thus increasing the inhibitory net charge associated with a single synaptic event. Block of K+ channels did not prevent the increase of decay time and charge. Protein kinase A (PKA) blocker KT5720 and pertussis toxin inhibited the action of baclofen, whereas 8Br-cAMP mimicked the GABAB R action. The same GABAB R-mediated modulation of GABAA Rs was observed in pyramidal neurons of rat temporal cortex, with both PKA and PKC involved in the process. In cortices from TLE patients and epileptic rats, baclofen lost its ability to modulate mIPSCs. Significance Our results highlight the association of TLE with functional changes of GABAergic signaling that may be related to seizure propagation, and suggest that the selective activation of a definite subset of nonpresynaptic GABAB Rs may be therapeutically useful in TLE.

Background and aims Phenylalanine (Phe) restricted diet, combined with Phe-free l -amino acid supplementation, is the mainstay of treatment for phenylketonuria (PKU). Being the diet a key factor modulating gut microbiota composition, the aim of the present paper was to compare dietary intakes, gut microbiota biodiversity and short chain fatty acids (SCFAs) production in children with PKU, on low-Phe diet, and in children with mild hyperphenylalaninemia (MHP), on unrestricted diet. Methods and Results We enrolled 21 PKU and 21 MHP children matched for gender, age and body mass index z-score. Dietary intakes, including glycemic index (GI) and glycemic load (GL), and fecal microbiota analyses, by means of denaturing gradient gel electrophoresis (DGGE) and Real-time PCR were assessed. Fecal SCFAs were quantified by gas chromatographic analysis. Results We observed an increased carbohydrate (% of total energy), fiber and vegetables intakes (g/day) in PKU compared with MHP children (p = 0.047), as well a higher daily GI and GL (maximum p Compared with MHP, PKU showed a lower degree of microbial diversity and a decrease in fecal butyrate content (p = 0.02). Accordingly, two of the most abundant butyrate-producing genera, Faecalibacterium spp. and Roseburia spp., were found significantly depleted in PKU children (p = 0.02 and p = 0.03, respectively). Conclusion The low-Phe diet, characterized by a higher carbohydrate intake, increases GI and GL, resulting in a different quality of substrates for microbial fermentation. Further analyses, thoroughly evaluating microbial species altered by PKU diet are needed to better investigate gut microbiota in PKU children and to eventually pave the way for pre/probiotic supplementations.

CD34+ circulating progenitor cells (CD34+CPCs) are a population of multipotent cells which can delay the development of atherosclerosis and cardiovascular disease (CVD) in conditions of increased CV risk. MicroRNAs (miRs) 221 and 222 modulate different genes regulating angiogenesis and inflammation; moreover, miR221/22 have beenshown to participate in differentiation and proliferation of CD34+CPCs, inhibiting cell migration and homing. miR221/222 in CD34+CPCs from hypertensive subjects are also increased and associated with CD34+cell number and reactive oxygen species (ROS). We evaluated CD34+CPC number, intracellular miR221/222 and ROS levels, arterial stiffness (AS)and echocardiography indices at baseline (T0).Then, after a six-month treatment with olmesartan, 20 mg/day (T1), in 57 hypertensive patients with left ventricular hypertrophy (LVH) and with no additional risk factor for CVD, and in 29 healthy controls (baseline),fibrinogen, C-reactive protein (CRP), glucose and lipid profiles were also evaluated.At T1, blood pressure values, CRP and fibrinogen levels, ROS and miR221/222 were significantly decreased (all p

Vagal nerve stimulation (VNS) is a palliative treatment option for drug-resistant epilepsy. The aim of this study was to describe the clinical and demographic features of selected patients scheduled for VNS and to evaluate the long-term efficacy of VNS in seizure control.Between 2006 and 2013, 32 consecutive epileptic patients (14 male and 18 female) were enrolled at our Institute for VNS implantation. In all cases resective surgery had previously been excluded by the use of a noninvasive presurgical study protocol. Mean age was 32 years (range 18-50), and mean epilepsy duration 23 years (range 11-39). All subjects were followed-up for at least 2 years (mean 6 years, range 2-9) after VNS implantation. Patients were considered responders when a reduction of seizures of more than 50 % was reported.All patients had complex partial seizures, in 81 % of the patients with secondary generalization and in 56 % with drop attacks. Neurological examination revealed focal deficits in 19 % of the patients. Brain magnetic resonance imaging (MRI) was positive in 47 % of the patients. No surgical complications were observed in this series. Three patients were lost to follow-up. Twelve patients were classified as responders. Among the others, 1 patient experienced side effects (snoring and groaning during sleep) and the device was removed.Our data confirm that VNS is a safe procedure and a valid palliative treatment option for drug-resistant epileptic patients not suitable for resective surgery.

Objective The α 2 agonist dexmedetomidine (DEX) is an anesthetic agent that can provide sedation and analgesia without respiratory depression or changes in neuronal activity during microrecordings. The aim of our study was to confirm the efficacy and safety of anesthesia with DEX for unilateral deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease. Methods In 2013 and 2014, a series of 11 consecutive patients received continuous low-dose DEX infusion during unilateral deep brain stimulation of the STN. Intraoperative microrecordings, stimulation results, and patient reaction times in executing verbal and motor tasks were retrospectively analyzed. Functional outcomes were evaluated by comparing preoperative and 1-year postoperative Unified Parkinson's Disease Rating Scale Part III scores. Results Typical activity of the STN was recorded in all patients, and the delay in the execution of both motor and verbal tasks was ≤2 seconds. No hemorrhagic complications occurred, and no postoperative side effects were observed. The mean percentage of Unified Parkinson's Disease Rating Scale Part III improvement at last follow-up was 39.01% (range, 23.70%–55.60%). The mean percentage of levodopa equivalent dose reduction was 45.86% (range, 21.50%–65.70%). Conclusions The results of our study confirm that the use of DEX in managing patients with Parkinson disease during unilateral deep brain stimulation of the STN is safe and effective and can be considered a promising option for sedation during this type of procedure.

Background BK virus (BKV)-associated nephropathy (BKVAN) is often associated with renal graft dysfunction. When renal transplant recipients present with high clinical suspicion for BKVAN (high serum and urine BKV titer with graft dysfunction) but their graft biopsies stain negatively for BKV, non-correlated situations between the two tests often lead to a dilemma about how to treat them. Methods This retrospective investigation was conducted to determine how real-time quantitative PCR (qPCR) for BKV, routinely applied to serum and urine, could be helpful in identifying the existing BKV in biopsy tissue stained negatively for BKV. Results DNA was extracted from each specimen through the use of five 10-μm curls from the tissue block with use of the QIAamp DNA FFPE Tissue Kit (Qiagen), followed by BKV qPCR to determine copies of BKV/μg of biopsy tissue DNA. Group 1 (11 negative renal controls for BKV) demonstrated 0 to 9 BKV copies/μg DNA. Except for 3 focally staining cases showing low BKV, the remaining 10 positive renal controls in group 2 (13 positive transplant biopsies staining positively) demonstrated elevated BKV up to 160 million copies/μg DNA. Group 3 transplants (13 uncertain transplants with negative BKV staining but positive liquid BKV) were negative for BKV (0–12 copies/μg) in 4 of 13, had low BKV copies (36–346 copies/μg) in 5 of 13, and had high BKV copies (17,240–526,945 copies/μg) in 4 of 13 cases, through the use of qPCR. Conclusions The data indicate that qPCR from paraffin-embedded tissue as a backup test is sensitive for ruling in/out BKV infection in renal transplant biopsies, particularly in uncertain cases.

The presence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) was investigated using hybridization in 15 lymph nodes and one Kaposi's sarcoma skin lesion obtained from HIV-positive patients. Cryostat tissue sections were hybridized with chemically modified DNA probes for HBV and HIV. HIV genome was mainly observed in the cytoplasm of cells present in 7 15 lymph nodes and in the Kaposi's sarcoma skin lesion, thus indicating the expression of HIV replication. Control samples hybridized with an HTLV I probe were negative. HBV genome was found in the cytoplasm of lymphoid mononuclear cells in 2 7 lymph nodes, obtained from HIV+ patients without serum markers of ongoing HBV infection. Lymph node positivity for HBV DNA also confirms that lymphoid cells may be a target for HBV. Since HBV infection seems to precede HIV infection in nearly all patients, it is possible that it may represent a factor facilitating the development of the HIV-related disease.

An altered gut microbiota has been linked to obesity in adulthood, although little is known about childhood obesity. The aim of this study was to characterize the composition of the gut microbiota in obese (n = 42) and normal-weight (n = 36) children aged 6 to 16. Using 16S rRNA gene-targeted sequencing, we evaluated taxa with differential abundance according to age- and sex-normalized body mass index (BMI z-score). Obesity was associated with an altered gut microbiota characterized by elevated levels of Firmicutes and depleted levels of Bacteroidetes. Correlation network analysis revealed that the gut microbiota of obese children also had increased correlation density and clustering of operational taxonomic units (OTUs). Members of the Bacteroidetes were generally better predictors of BMI z-score and obesity than Firmicutes, which was likely due to discordant responses of Firmicutes OTUs. In accordance with these observations, the main metabolites produced by gut bacteria, short chain fatty acids (SCFAs), were higher in obese children, suggesting elevated substrate utilisation. Multiple taxa were correlated with SCFA levels, reinforcing the tight link between the microbiota, SCFAs and obesity. Our results suggest that gut microbiota dysbiosis and elevated fermentation activity may be involved in the etiology of childhood obesity.

Circulating progenitor cells (CPCs) represent a pool of cells capable of differentiating into mature cells of different organs and systems, promoting tissue maintenance and repair. Among CPCs, CD34 + cells (CD34 + CPCs) seem to predict outcome in CV disease, also in elderly people. A decline in CD34 + CPCs was reported with advancing age. Moreover, aging is associated with a state of chronic inflammation, influencing life expectancy. Our purpose was to investigate a 10-year predictive ability of CD34 + CPCs, inflammatory marker levels, classic CV risk factors (CVRFs), and Framingham Risk Score (FRS) in a population of healthy, self-sufficient octogenarians. We found that baseline CD34 + CPCs was strongly associated with mortality, showing a significant difference in CD34 + CPC numbers between deceased and living patients. Moreover, by dividing our patients into tertiles based on age reached, this difference was more remarkable the higher the age reached. Regressive analyses suggested that the chances of reaching an older age depend on higher CD34 + CPCs at baseline and are not significantly affected by inflammatory markers levels, FRS, CVFRs, or HDL-C levels. We found that higher CD34 + CPCs predict longer life also in the oldest old, providing additional insights on the predictive role of CD34 + CPCs in subjects aged 80 years or more.

Background Treatment choice for chronic HBV infection is a continuously evolving issue, with a wide range of options. We aimed to evaluate the current practice of HBV therapies in the real world in Southern Italy. Methods A prospective study enrolling over a six month period (February–July 2010) all consecutive HBsAg positive subjects, never previously treated, referred to 16 liver units in two Southern Italy regions (Calabria and Sicily). Results Out of 247 subjects evaluated, 116 (46.9%) had HBV-DNA undetectable or lower than 2000 UI/ml. There were 108 (43.7%) inactive carriers, 103 (41.7%) chronic hepatitis, and 36 (14.6%) liver cirrhosis. Antiviral treatment was planned in 94 (38.0%) patients (26 cases with Interferon or Pegylated Interferon and 68 with nucleos(t)ides analogues). As many as 49.5% of subjects with chronic hepatitis did not receive antiviral treatment. Discussion The majority of chronic HBsAg carrier referring centres for evaluation were not considered suitable for antiviral treatment. Nucleos(t)ides analogues are the preferred first choice for therapy. A long-lasting period of observation may be needed to make appropriate therapeutic decisions in several cases.

Abnormally viscous bronchial secretions, a characteristic feature of cystic fibrosis (CF), may trap bacteria and fungi, allowing transient or chronic lung colonization. We report here a case of persistent Scedosporium apiospermum colonization in a patient with CF, who subsequently developed a lung mycetoma, and died with neurological symptoms suggestive of cerebral fungal involvement. Six isolates from consecutive sputum samples were molecularly typed by random amplification of polymorphic DNA (RAPD) using primers UBC701, UBC703, and GC70. Moreover, in vitro susceptibility of these isolates to current antifungals (amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and anidulafungin) was investigated by means of both E-test and CLSI methods. Antifungal susceptibility testing showed low minimum inhibitory concentration values only for triazole drugs. However, a unique genotype was isolated over a 12-month period, despite antifungal treatment with voriconazole for three months. This case report illustrates the therapy-refractory feature of this fungus, and provides new evidence that, as already reported, once a genotype of S. apiospermum has established colonization, it seems not to be replaced by others.

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically changed over the past 10 y with the emergence of community-associated MRSA (CA-MRSA). Recent studies have reported a frequent association of these strains with hospital outbreaks, and an incidence varying over time and by region. In order to evaluate the MRSA lineages circulating in our area of Italy, we performed a molecular characterization of CA-MRSA isolates prospectively collected from April 2006 to July 2007 at the San Paolo Hospital of Milan. We investigated the protein A-encoding gene (spa-typing), the staphylococcal chromosomal cassette SCCmec, the presence of Panton-Valentine leukocidin (PVL), and 3 adhesin genes. Twenty-five CA-MRSA isolates cultured from 25 patients were collected; an equal number of healthcare-associated (HA)-MRSA strains, from 25 patients hospitalized in various wards, were collected for comparison purposes. SCCmec type IV emerged as the most frequent genotype in both CA- and HA-MRSA. Seventeen different spa types were identified: t515 was the most common (36%), followed by t008 (20%). We detected 3 PVL-positive strains, only among the CA-MRSA. On the whole, our local MRSA epidemiology appears to be heterogeneous, with a predominant t515 spa type, only recently considered to belong to clonal EMRSA-15.

The relation between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is not clearly defined. Some investigators suggest that patients with extensive colitis have a genetic predisposition to CRC and that long-standing inflammation is not of primary importance in the promotion of cancer. We have assessed any increased risk of colon cancer in the relatives of IBD patients. We studied the prevalence of malignancy in the relatives of 251 IBD patients [198 ulcerative colitis (UC); 53 Crohn's disease of the colon (CDC)] and 251 orthopedic patients (ORTHO) as controls. In all patients (UC, CDC) as well as in controls (ORTHO) the prevalence of colon, extracolic digestive and extradigestive malignant tumors in the first-degree relatives was evaluated. We found no significant difference in the number of colorectal tumors or of tumors of any other kind in the diverse group of relatives of patients with IBD and ORTHO patients. Our data do not point to the existence of hereditary factors linking UC or CDC to CRC.

Objective In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1–2, BA1–2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. Methods ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. Results Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1–2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. Conclusion Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. Significance Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients.

Background/Aims In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. Methods We conducted an epidemiological investigation, including a case-control study, to identify the source and the modes of HAV transmission. Hepatitis B and C (HCV) viruses and human immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence analysis of the VP1/2A junction of the HAV isolates was also performed. Results Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was contact (not related to injecting practices) with a jaundiced person (odds ratio: 5.8; 95% confidence interval: 1.3–29.9). Of the cases, 58% were anti-HCV positive and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype IB (8 cases) and IIIA (7 cases) were detected. Conclusions HAV was probably transmitted through the fecal-oral route, although parenteral transmission cannot be excluded. The high fatality rate was probably due to severe underlying liver damage. The occurrence of this outbreak highlights the need for routine HAV vaccination for IDUs.

We present an initial report regarding the clinical usefulness of peroral cholangioscopy, using a new type of cholangioscope, the Polyscope. Peroral cholangioscopy was performed in four patients with strictures after orthotopic liver transplantation (OLT) which were suspected of being ischemic biliary lesions, in three with indeterminate biliary strictures, in three with suspected retained bile duct stones, and in two for evaluation of the intraductal spread of adenomatous tissue after an ampullectomy. In all cases peroral cholangioscopy was performed successfully without complications. On the basis of direct viewing and/or tissue sampling a correct diagnosis was reached in all cases: in all patients who underwent OLT the strictures were not ischemic; the indeterminate strictures were all benign; and, in patients with suspected stones, complete clearance was confirmed. Intraductal spread was confirmed in one patient and excluded in the other. In our experience, peroral cholangioscopy using a Polyscope is a safe and effective method for diagnosing bile duct lesions. © Georg Thieme Verlag KG Stuttgart - New York.

Object Although neuroendoscopic biopsy is routinely performed, the safety and validity of this procedure has been studied only in small numbers of patients in single-center reports. The Section of Neuroendoscopy of the Italian Neurosurgical Society invited some of its members to review their own experience, gathering a sufficient number of cases for a wide analysis. Methods Retrospective data were collected by 7 centers routinely performing neuroendoscopic biopsies over a period of 10 years. Sixty patients with newly diagnosed intraventricular and paraventricular tumors were included. No patient harboring a colloid cyst was included. Data regarding clinical presentation, neuroimaging findings, operative techniques, pathological diagnosis, postoperative complications, and subsequent therapy were analyzed. Results In all patients, a neuroendoscopic tumor biopsy was performed. In 38 patients (64%), obstructive hydrocephalus was present. In addition to the tumor biopsy, 32 patients (53%) underwent endoscopic third ventriculostomy (ETV), and 7 (12%) underwent septum pellucidotomy. Only 2 patients required a ventriculoperitoneal shunt shortly after the endoscopy procedure because ETV was not feasible. The major complication due to the endoscopy procedure was ventricular hemorrhage noted on the postoperative images in 8 cases (13%). Only 2 patients were symptomatic and required medical therapy. Infection occurred in only 1 case, and the other complications were all reversible. In no case did clinically significant sequelae affect the patient's outcome. Tumor types ranged across the spectrum and included glioma (low- and high-grade [27%]), pure germinoma (15%), pineal parenchymal tumor (12%), primary neuroectodermal tumor (4%), lymphoma (9%), metastasis (4%), craniopharyngioma (6%), and other tumor types (13%). In 10% of patients, the pathological findings were inconclusive. According to diagnosis, specific therapy was performed in 35% of patients: 17% underwent microsurgical removal, and 18% underwent chemotherapy or radiotherapy. Conclusions This is one of the largest series confirming the safety and validity of the neuroendoscopic biopsy procedure. Complications were relatively low (about 13%), and they were all reversible. Neuroendoscopic biopsy provided meaningful pathological data in 90% of patients, making subsequent tumor therapy feasible. Cerebrospinal fluid pathways can be restored by ETV or septum pellucidotomy (65%) to control intracranial hypertension. In light of the results obtained, a neuroendoscopic biopsy should be considered a possible alternative to the stereotactic biopsy in the diagnosis and treatment of ventricular or paraventricular tumors. Furthermore, it could be the only surgical procedure necessary for the treatment of selected tumors.

Background: The recently discovered TT virus (TTV) has been shown to be highly prevalent in patients with cryptogenetic chronic liver disease and fulminant hepatitis. To study the frequency of TTV and to evaluate the possible association with liver disease, 37 pediatric and young adult patients with thalassemia, and 36 healthy children were included in the study. The sera of 100 blood donors selected randomly in the same period were also tested for TTV DNA. Methods: The TTV amplification by polymerase chain reaction (PCR) was performed using a first set of primers that recognize an internal sequence into N22 and a second set of primers amplifying a sequence within 5'NCR (5' noncoding region). Results: The first set of primers revealed TTV DNA in 73% of thalassemic patients, in 8% of healthy children, and in 5% of healthy blood donors. With the second set of primers, the prevalence of TTV DNA was, respectively, 100% in thalassemic patients, 44.5% in healthy pediatric patients, and 87% in healthy blood donors. All individuals who tested positive for TTV by the first set of primers were also positive by the second primer set. The TTV infection seemed not to be the cause of altered transaminase levels. Sequencing of TTV clones from thalassemic patients showed the presence of different TTV variants in the same serum. Conclusion: The prevalence of TTV in polytransfused children is similar to that detected in blood donors. Moreover, TTV can be detected in healthy children of all ages. The presence of TTV seems to have no clinical significance.

Technical complications and nosocomial bloodstream infections associated with short-term central venous catheterization remain a heavy burden in terms of morbidity, mortality and cost in HIV-positive subjects. Between 1994 and 1997, 327 central venous catheters (CVCs) inserted in 212 patients for a total of 5005 catheter days were investigated. Forty-two technical complications (13%) occurred in 40 patients. Logistic regression analysis revealed that a high APACHE III score was associated with development of CVC-related complications (P = 0.01). One hundred and eight of 327 CVCs (33%) were suspected as being infected. However only 61 episodes (61/327, 19%) were finally diagnosed as CVC-related sepsis. Three variables affecting the rate of CVC-related sepsis were identified: 1) administration of TPN (P = 0.01); 2) low number of circulating CD4+ cells (P = 0.04); 3) high APACHE III score (P = 0. 04). Doctors responsible for AIDS patients should carefully consider the relative risks and benefits of CVC insertion in an individual patient.

The epidemiological features of 37 episodes of candidemia in HIV-infected subjects were analysed in a retrospective matched case-control study conducted over an 8-year period (1990-1997). Univariate analysis identified eight risk factors that were significantly associated with candidemia (P0.05): i) use of central venous catheters; ii) administration of total parenteral nutrition; iii) previous antifungal therapy; iv) previous therapy with glycopeptides; v) presence of oral/ esophageal candidiasis; vi) concomitant bacterial infections; vii) neutropenia; and viii) concomitant AIDS dementia complex. Stepwise logistic regression analysis revealed that the only independent risk factor for developing candidemia was the use of central venous catheters (P = 0.0001). Candida albicans was the most frequently isolated pathogen, accounting for 18 (48%) episodes of candidemia, followed by Candida tropicalis (19%) and Candida glabrata (11%). The crude mortality rate was 62%. On univariate analysis concomitant opportunistic infections, presence of non-Candida albicans species of Candida and neutropenia were shown to be predictive of death. Multivariate analysis revealed that the presence of non-Candida albicans strains of Candida was the only significant factor associated with a worse prognosis (P = 0.001). In conclusion, candidemia appears to be more common in patients with advanced HIV disease. Of the factors which influenced the onset of candidemia, use of central venous catheters seemed to be the most important one.

This study was conducted to evaluate the efficacy of highly active anti-retroviral therapy (HAART) in preventing recurrence of oral candidosis (OC) associated with HIV. A prospective case-controlled observational study was performed in an inner-city university-hospital HIV/AIDS clinic. Ninety-three HIV-positive study subjects with a history of recurrent OC were divided into two groups: protease inhibitors (PI)-treated patients (group 1, n = 30) and non-PI-treated patients (group 2, n = 63). Study subjects were matched for sex, age, stage of HIV infection, and peripheral CD4+ T-cell counts. The non-PI-treated group was further subdivided into the following three subgroups: HIV-positive study subjects treated with reverse transcriptase inhibitors (RTI; groups 2a and 2c) and HIV-positive study subjects not treated with RTIs (group 2b). Group 2c met the same inclusion criteria as group 2a had but was matched 6 months after the beginning of the study. We also assessed in vitro peripheral blood mononuclear cells (PBMC) and their lymphoproliferative response, as well as cutaneous delayed-type hypersensitivity (DTH) response to Candida-associated antigens in a randomly selected sample of study subjects divided into those treated with PIs and those who were not. During a 1-year follow-up, OC was diagnosed in 2 (7%) PI-treated and 23 (36%) non-PI-treated patients (p

Microsurgical resection, stereotactic aspiration and VP shunt have for years been the choice options for the treatment of colloid cysts of the third ventricle. Recently, endoscopic approaches have aroused increasing interest and gained acceptance. Although safer, this minimally invasive approach is considered less efficacious than microsurgery. Relatively long-term results are now available and some conclusions might be inferred on the usefulness of this procedure. Between 1994 and 2005, 61 patients harbouring a colloid cyst of the third ventricle were treated with neuroendoscopic technique in 11 Italian neurosurgical centres. Cyst diameters ranged from 6 to 32 mm. A flexible endoscope was used in 34 cases, a rigid one in 21, both instruments in six. The technique consisted in cyst fenestrations, colloid aspiration, coagulation of the internal cyst wall and, occasionally, capsule excision. Mean postoperative hospital stay was 6.7 days. Early postoperative neuroimaging revealed a cyst residue in 36 cases (mean diameter 4.3 mm). There were two complications (3.2%). Follow-up varied between 1 and 132 months (mean 32 months, more than 5 years in 17 patients). There were seven asymptomatic recurrences, three of them evolving from a previous residue. The endoscopic approach to the treatment of colloid cysts is safe, effective and well accepted by patients. Although asymptomatic, recurrences (11.4%) cast a persisting shadow on the long-term results, and, therefore, the controversy with the traditional microsurgical treatment remains open.

A Rhodococcus equi pulmonary infection in a 63-year-old man receiving chemotherapy and radiotherapy for spinocellular carcinoma is described. The patient, a knife-grinder, was promptly treated with levofloxacin plus amikacin followed by rifampicin for 2 months, and he is still in good clinical condition after an 8-month follow-up.

Fully covered self-expanding metal stents (FCSEMSs) are now being used to treat postoperative biliary strictures (BSs) and biliary leaks (BLs). The aim of this study was to assess the safety and effectiveness of a new FCSEMS (Wallflex) in patients with postoperative BSs and BLs after failure of traditional endoscopic treatment. Between January 2010 and December 2011, 16 patients (10 patients with postcholecystectomy BSs, 4 with postcholecystectomy BLs, and 2 with postorthotopic liver transplantation BSs) were enrolled. The technical and clinical success rate was 100%. All FCSEMSs were removed after a mean of 141 days. Complications occurred in 7 cases: 2 postprocedure pain, 2 mild pancreatitis, 1 early distal, and 2 late proximal FCSEMS migration. The overall long-term clinical success rate was 94% after a mean follow-up of 13 months. In our experience, the placement of FCSEMSs is an effective and secure method of treating refractory postoperative BSs or BLs.

The objective of this case-control study, conducted in a large Italian university hospital over a 12-month period, was to evaluate the risk factors associated with the emergence of azole resistant oral candidosis in 64 Human Immunodeficiency Virus (HIV) infected patients. A swab was obtained from each patient by brushing candidal lesions. Candida albicans was isolated in 41 patients (64%), Candida glabrata in ten (16%), Candida krusei in five (8%), Candida kefyr in two (3%), Candida tropicalis in two (3%), and Candida lipolytica and Candida guilliermondii in one case, respectively. Two patients suffered a double infection i.e. C. albicans + C. krusei and C. albicans + C. glabrata, respectively. Candida species were tested in vitro for their susceptibility to ketoconazole, fluconazole, itraconazole and amphotericin B. MICs of the four antifungal drugs were obtained for each yeast using a microdilution broth method developed in our laboratory. Twenty four (37%) of the isolated strains were resistant both to itraconazole and fluconazole, five (8%) to fluconazole alone, and two (3%) to ketoconazole alone, while none of the isolated strains was resistant to amphotericin B. Patients with oral candidosis caused by a strain resistant to one or more azole drug were compared to control patients with azole-susceptible oral candidosis. On univariate analysis, more than five episodes of oral candidosis in the last year (P = 0.01), previous use of azole therapy (P = 0.001), C2-3 category of HIV infection (P = 0.01) and low number of circulating CD4+ T-cells (P = 0.03) were significantly associated with an increased risk for the development of azole resistance. However, previous use of azole therapy was the only factor selected by a stepwise logistic regression analysis which was independently associated with the isolation of azole resistant strains (P = 0.003). Our findings indicate that, in view of the potential risk for the emergence and selection of azole resistant strains of Candida in patients with AIDS, it is important to carefully choose the antifungal drug for the therapy of mild fungal infections after evaluation of the in-vitro susceptibility of the isolated strains.

Background & Aims: The yeast Hansenula anomala has been associated with gastrointestinal symptomatology and damage to the intestinal wall in humans. In vitro and in vivo, H. anomala secretes a toxin, killer toxin, which is lethal to other microorganisms. In view of the very high rate of killer phenotype expression recorded for H. anomala strains in nature, this study aimed to investigate the hypothesis that H. anomala killer toxin plays a role in the pathogenesis of H. anomala -induced enteritis. Methods: Effects of active and heat-inactivated H. anomala killer toxin on intestinal fluid homeostasis and electrolyte balance were investigated in rat small intestine using a standard intestinal perfusion technique. Sections of the perfused jejunum tracts were examined histologically. Results: H. anomala killer toxin induced a significant secretion of water and electrolytes. No significant change was observed when either heat-inactivated H. anomala killer toxin or control growth medium were tested. Histological analysis showed ischemic degeneration of villi and sloughing of surface epithelium in 50% of active H. anomala killer toxin-perfused jejuna. Conclusions: This paper presents original observations compatible with the hypothesis that H. anomala killer toxin plays a role in the pathogenesis of H. anomala -induced enteritis.

Background Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. The utility of serum alpha-fetoprotein (α-FP) in its detection is questionable. Over-expression and high circulating levels of insulin-like growth factor-II (IGF-II) were reported in tissue and in serum of patients with HCC. We investigated the diagnostic application of IGF-II in the diagnosis of HCC. Methods Serum IGF-II and α-FP levels were measured in 178 patients (82 with HCC and 96 with liver cirrhosis) and in 30 healthy controls. Spearman test, non parametric combination test and confidence interval analysis were used for statistical evaluation of data. Results The best cut-off values selected by ROC curves were 796 ng/ml for IGF-II and 132 ng/ml for α-FP. IGF-II mean values were higher in patients with HCC than in those with liver cirrhosis (LC) ( p = 0.0001) but lower in LC than in controls ( p = 0.0001). Serum IGF-II levels above cut-off were found in 22% of patients with HCC, in 9.3% of those with cirrhosis and in 20% of controls. α-FP serum levels > 132 ng/ml were observed in 48% of HCC, in 3.1% of LC and in none of control group. By correlation study, serum IGF-II levels were significantly correlated with serum α-FP levels ( r = 0.427, p = 0.0001) and with nodules' diameter ( r = 0.252, p = 0.0130) but not with nodules' number ( p > 0.050). Finally, IGF-II showed lower sensitivity, specificity and predictive values than α-FP. Conclusion Circulating IGF-II is not a useful marker for HCC. Further researches are however needed to evaluate its diagnostic accuracy before and after nutritional adjustment.

KIAA1549-BRAF fusion gene and isocitrate dehydrogenase (IDH) mutations are considered two mutually exclusive genetic events in pilocytic astrocytomas and diffuse gliomas, respectively. We investigated the presence of the KIAA1549-BRAF fusion gene in conjunction with IDH mutations and 1p/19q loss in 185 adult diffuse gliomas. Moreover BRAF(v600E) mutation was also screened. The KIAA1549-BRAF fusion gene was evaluated by reverse-transcription polymerase chain reaction (RT-PCR) and sequencing. We found IDH mutations in 125 out 175 cases (71.4%). There were KIAA1549-BRAF fusion gene in 17 out of 180 (9.4%) cases and BRAF(v600E) in 2 out of 133 (1.5%) cases. In 11 of these 17 cases, both IDH mutations and the KIAA1549-BRAF fusion were present, as independent molecular events. Moreover, 6 of 17 cases showed co-presence of 1p/19q loss, IDH mutations and KIAA1549-BRAF fusion. Among the 17 cases with KIAA1549-BRAF fusion gene 15 (88.2%) were oligodendroglial neoplasms. Similarly, the two cases with BRAF(v600E) mutation were both oligodendroglioma and one had IDH mutations and 1p/19q co-deletion. Our results suggest that in a small fraction of diffuse gliomas, KIAA1549-BRAF fusion gene and BRAF(v600E) mutation may be responsible for deregulation of the Ras-RAF-ERK signaling pathway. Such alterations are more frequent in oligodendroglial neoplasm and may be co-present with IDH mutations and 1p/19q loss.

Various types of self-expandable metal stents have been introduced for the palliation of malignant biliary obstruction.To compare the outcomes of WallFlex™ and Wallstent™ uncovered biliary self-expandable metal stents (SEMSs) for the palliation of patients with malignant biliary obstruction.Between October 2008 and December 2009, all SEMSs placed for malignant biliary obstruction were WallFlex™: all patients palliated were included in the study. Before October 2008, all the SEMSs placed for malignant biliary obstruction were Wallstent™, and the patients palliated from July 2007 to September 2008 were the comparative group.A total of 58 WallFlex™ and 54 Wallstent™ SEMSs were placed, and efficacious biliary decompression was achieved in all patients. Early complications occurred in 5 patients in the WallFlex™ group and in 3 in the Wallstent™ group (p=ns). Late complications occurred in 6 patients in the WallFlex™ group and in 16 in the Wallstent™ group (p0.01). The overall patency of the self-expandable metal stent in the WallFlex™ and the Wallstent™ groups was similar (227 days vs. 215 days, p=ns). Mean patient survival was 242 days in the WallFlex™ group and 257 days in the Wallstent™ group (p=ns).We found no difference in terms of overall patency between the two types of SEMSs, but there was an increased rate of late adverse events in the Wallstent™ group.

Background Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) of unknown aetiology. The ‘hygiene hypothesis’ (HH) suggests that several hygiene-related factors may have contributed to the increased incidence of IBD. The aim of the study was to evaluate risk factors for IBD related to HH in a cohort of IBD patients from the south of Italy. Methods We prospectively performed a one-year, questionnaire-based, case–control, multi-centre study focusing on the principal risk factors for IBD according to HH. We investigated the main surrogate markers of HH (helmintic infections and antibiotics in childhood; breastfeeding; family size/sibship;urban upbringing; personal and domestic hygiene in childhood) in UC and CD patients, in comparison with a control group of healthy subjects. In addition, the traditional risk factors for IBD were also recorded. Results The study population included 527 cases of UC, 468 CD and 562 controls. None of the surrogate risk factors of HH was significantly associated with IBD. On the contrary, the traditional risk factors confirmed their statistical significance in this IBD population. Familial aggregation: OR 4.07 for UC; OR 4.83 for CD; smoking: OR 0.38 for UC; OR 1.40 for CD; appendectomy: OR 0.28 for UC; OR 1.61 for CD. Conclusion Even though risk factors associated to the HH have been proposed as a possible explanation for the increasing calendar trend of IBD incidence, their role does not appear to be statistically significant. Familial aggregation, smoking habits and appendectomy still remain the main risk factors associated with IBD.

Video–EEG monitoring with intracranial subdural electrodes is a useful assessment tool for the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy. We aimed at assessing the morbidity related to electrode implantation and the surgical outcome in patients who underwent epilepsy surgery after intracranial EEG monitoring. All patients (N = 58) admitted to our Epilepsy Surgery Centre for drug-resistant focal epilepsy who underwent resective surgery after intracranial monitoring with subdural electrodes and were followed up for at least 2 years were included in the study. Their mean age was 30.4 years (range 8–60 years), 25 (43 %) were female, and 44 (76 %) had a preoperatively detected structural lesion. The mean duration of invasive recording was 2.3 days (range 1–14 days). Extraoperative ECoG allowed the identification of the epileptogenic focus in all cases. The temporal lobe was involved in 21 (36 %) patients, whereas extratemporal foci were identified in 24 (41 %) patients. Thirteen patients (23 %) had multilobar involvement. Functional brain mapping was performed in 15 (26 %) patients. Transient complications related to electrode implantation occurred in three patients. Among patients with evidence of lesion on preoperative MRI, lesionectomy alone was performed in 12 cases (27 %), while it was combined with tailored cortical resection in the remaining cases. Tailored cortical resection was also performed in patients without evidence of lesion on MRI. After resective surgery, transient neurological deficits occurred in five cases, while another patient experienced permanent lateral homonymous hemianopia. At the last follow-up observation, 34 (57 %) patients were seizure-free (Engel class I). This study suggests that invasive EEG recording with subdural electrodes may be useful and fairly safe for many candidates for epilepsy surgery.

The aim of this study was to evaluate the outcomes of through-the-scope (TTS) large diameter self-expanding metal stent (SEMS) placement for palliation of malignant colorectal obstruction.Between January 2005 and December 2009, all patients who underwent endoscopic SEMS placement for palliation of malignant colorectal obstruction were prospectively enrolled.Thirty-nine patients (17M and 22F; mean age 75.9 ± 10.6 years, range 50-91) were enrolled. The most frequent location was the sigmoid colon (13 cases). The causes of obstruction were colorectal malignancy in 32 patients and extracolonic malignancy in 7. Technical success was achieved in 36/39 patients (92.3%) and clinical success in 35/39 patients (89.7%). Technical failure was related to female sex (p = 0.04) and the extracolonic etiology of the stricture (p0.001). There were three early complications: two procedure-related perforations successfully managed conservatively and one hemorrhage treated with APC. Early complications were related to the location of strictures at the recto-sigmoid junction (p0.001). Late complications occurred in 10 patients: 8 of these patients experienced occlusive symptoms (attributable to tumor ingrowth in 5 cases and stool impaction in 3 cases); the remaining 2 were one case of tumor ingrowth with sub-occlusive symptoms and hemorrhage, and one case of distal migration. There was no procedure-related mortality and all complications were managed without surgical intervention. SEMS patency duration was 236 ± 128 days (range 31-497) and mean survival of the patients was 259 ± 121 days (range, 32-511).In our experience, TTS large-diameter SEMS placement is a safe and effective treatment for palliation of malignant colorectal obstruction.

Objective Capillary hemangiomas are benign vascular lesions involving the skin and soft tissues that commonly occur at birth or an early age. Intracranial capillary hemangiomas are extremely rare; only 14 cases have been reported the literature. Case Description We describe four patients with capillary hemangiomas. In two of these patients the lesions arose from the cavernous sinus. In the third patient, a large capillary hemangioma arising from the middle cranial fossa extended into the infratemporal fossa. The fourth patient had a left hemorrhagic temporoparietal capillary hemangioma. Results The first two patients underwent a partial resection, followed by radiotherapy. Local tumor control was achieved in both cases, as shown by the follow-up magnetic resonance imaging. In the third patient the lesion was subtotally removed after embolization. Radiotherapy, performed one year after surgery because of recurrence, allowed tumor control. In the fourth patient surgical removal was total and no adjuvant radiotherapy was required after surgery; follow-up magnetic resonance imaging did not show any recurrence at the one-year follow-up. Conclusion Surgery is an option for symptomatic intracranial capillary hemangiomas. However, because partial removal is associated with a high recurrence rate, capillary hemangiomas that cannot be removed radically should be treated with radiotherapy, which offers the possibility of controlling lesion size and preventing tumor recurrence.