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Purpose The aim of this study is to compare the use of 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) in IV ventricular ependymoma (IVEP) surgical resection. Methods In this retrospective study, six patients with IVEP were enrolled. Gender ratio 2:1 male to female, with mean age 38.9 years old. A 5-ALA oral dose of 20 mg/kg and a SF intravenous dose of 2 mg/kg were administered. Telo-velar approach, operative microscope, and intraoperative monitoring were used in all the operations. We retrospectively compared the two fluorescence techniques at four steps during the surgical procedure: step 1: exposure of the tumor; step 2: dissection of the lesion from the cerebellum; step 3: assessment of the tumor borders and differentiation from normal tissue at the base of implants; and step 4: evaluation of possible residual tissue in the surgical cavity. Results At the first step, the ependymomas resulted well delineated by both fluorescent agents. In this step, 5-ALA was particularly helpful in the case of recurrent ependymoma. At step 2, 5-ALA provided a better identification of the ependymoma boundaries and distinction from cerebellum hemispheres than SF. In steps 3 and 4, SF was really helpful to detect tumor tissue. Conclusion According to our experience, fluorescence-guided surgery of IVEP with 5-ALA and SF is useful to maximize surgical resection with less risk of brainstem injury. Both fluorescence techniques are helpful in different steps of IVEP resection. However, further studies are needed to confirm our preliminary data.

Tumours of the anterior visual pathways are challenging to operate because of the crucial balance between extent of resection and sight preservation. Sodium Fluoresceine (SF) has already been reported in maximizing brain tumour resection but not when the optic-chiasmatic region is involved. The role of Visual Evoked Potentials (VEPs) in optic-chiasmatic tumours is still debated. The simultaneous use of both technique in this setting has not been reported so far. The aim of our work is to analyse the intraoperative combination of the use of SF and VEPs in the anterior visual pathway tumour surgery.Clinical and Intra-operative data from six surgical procedures on four patients affected by optic-chiasmatic tumours with preoperative visual deficits were retrospectively analysed.In 5 procedures VEPs remained intraoperatively stable and no postoperative worsening of visual function was reported. In 1 case an intraoperative VEPs deterioration was predictive of a postoperative visual worsening. In all cases, tumour was fluorescent, and SF was intraoperatively helpful in guiding resection. The pattern of fluorescence was different according to the lesion histology.Based on our preliminary experience, the simultaneous combination of SF and VEPs in surgery of the optic pathway tumours seems helpful to maximize tumour resection and predict postoperative functional outcome. Since we presented a small series, larger studies are needed to confirm our data.

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Background The submental artery island flap is widely used in head and neck reconstruction, since it is easy and quick to harvest, and it can be successfully used for the coverage of perioral, intraoral and facial defects. We used this technique for the reconstruction of a complex soft-tissue and bony defect of rhino-oropharinx. Case report Osteoradionecrosis of rhino-oropharingeal posterior wall with C2 necrotic body exposure occurred in a 77-year-old woman. After the failure of reconstruction with a Hadad-Bassagasteguy flap, a submental island flap with cervical spine stabilization was planned to be performed in a one-stage operation. The anterior arc of C1 and odontoid process of C2 were removed and, according to the defect size, a submental island flap was designed in an elliptical fashion. The flap was rotated 180° and tunnelized under the left parapharingeal-prevertebral space, then it was positioned in the rhino-oropharinx and fixed with reabsorbable sutures. The donor site was closed primarily. No peri- or post-operative complications occurred, neither in the recipient nor in the donor-site. At the latest follow-up, 15 months postoperatively, the patient was able to speak without any impairment and started swallowing rehabilitation with good results and an aesthetically satisfactory outcome. Conclusion The submental island flap may be a reliable and versatile flap for reconstruction of head and neck defects, even though in the rhino-oropharingeal posterior wall.

Background The introduction of exoscopes in neurosurgery has been welcomed due to their maneuverability, ergonomics, and low-profile frame. 3D devices have further enabled a better stereoscopic visualization. Reports on their application, albeit more and more frequent, are still at their beginning stages. We present our experience with the Olympus ORBEYE 4K-3D exoscope for major cranial procedures. The strengths and weaknesses of the exoscope are presented, and the nuances associated with the learning curve are illustrated. Methods Over 2 weeks, patients undergoing surgery for major cranial pathologies were offered to participate in this evaluation of the Olympus ORBEYE 4K-3D exoscope. Information on the use of the exoscope was collected to assess the features and struggles in the learning curve. A comparison with the operating microscope was made. Results Fourteen patients with different intracranial pathologies were operated on with the exoscope. No surgery-related complications occurred. The microsurgical part was performed with the exoscope in six cases. The exoscope was used for 72.9% (±37.5%) of the whole microsurgical time vs. 27.1% (±37.5%) microscope time (p = 0.02). Conclusion The Olympus ORBEYE 4K-3D exoscope represents a useful evolution of the operating microscope. It requires time to overcome potential difficulties, mostly related to previous motor schemes acquired with operating microscopes. Its features could represent the basis for a paradigm shift in microsurgery.

Il conteggio assoluto dei linfociti CD4+, un indicatore importante dello stato immunitario, e utile nel monitoraggio dei pazienti con infezione da HIV ed e stato utilizzato per molti anni come criterio decisionale per l’inizio della terapia. La condivisione di raccomandazioni Evidence Based da parte delle UU.OO. Malattie Infettive dell’AUSL Romagna ha diminuito la frequenza del monitoraggio citofluorimetrico e la spesa per reagenti e aumentato l’appropriatezza. Scopo dello studio e stato valutare se una riduzione del conteggio dei CD4+ in una coorte di pazienti HIV+ in trattamento con terapia antiretrovirale abbia aumentato la frequenza di eventi clinici maggiori, come lo sviluppo di patologie AIDS defining. Poiche il monitoraggio dei linfociti CD4+ nella maggior parte dei pazienti HIV+ seguiti in Romagna e effettuato in un unico Laboratorio, e possibile verificare se l’esecuzione di un numero minore di esami (indicatore di esito economico) sia associata a eventi AIDS defining nei pazienti con carica virale soppressa da oltre 2 anni (indicatore di esito clinico maggiore). In seguito all’adozione da parte degli infettivologi delle linee guida evidence based relative alle modalita di richiesta, sono stati raccolti (studio retrospettivo) i seguenti dati: numero di test CD4+ eseguiti, costo reagenti, aderenza alle raccomandazioni stesse. Dal 2014 al 2017 il numero dei conteggi CD4+ eseguiti per monitoraggio e diminuito del 61% (8476 analisi nel 2014, 5718 analisi nel 2015, 4217 analisi nel 2016 e 3250 nel 2017) senza alcuna segnalazione di eventi AIDS defining associata alla riduzione della frequenza della conta dei linfociti CD4 da parte dei clinici e con un risparmio del costo dei reagenti pari a 139.607 euro (−150%). Un monitoraggio citofluorimetrico dei linfociti CD4+ meno frequente nei pazienti HIV+ con carica virale soppressa stabilmente riduce la spesa del Laboratorio senza aumentare il rischio di sviluppare patologie AIDS defining.

BACKGROUND The incidence of asymptomatic colloid cysts is increasing due to the widespread use of neuroimaging tools. According to previous works, familial forms (within first-degree relatives) represent 5-25% of the cases, and it is not clear whether they display specific features influencing the clinical behavior of the disease. METHODS We reviewed the literature to extract data from papers dealing with familial colloid cysts. For comparison, previous series dealing with the natural history of sporadic cases were identified. Also, we present two more cases of familiar colloid cysts from our experience. RESULTS Fifty-one patients (23 reports, plus our cases) were analyzed. Familial cases showed a younger age at diagnosis (p=0.02) and fewer asymptomatic cases (p

Introduction Fluorescence guided surgery with 5-aminolevulinic acid (5-ALA) is a well-established technique for improving resection of malignant cerebral glioma. In recent years, this technique is being increasingly applied off label to other brain tumor entities such as Low-grade glioma, meningioma, metastases, lymphoma and other central nervous system tumors. In this paper We collected all the data of 5-ALA guided surgery in "not malignant glioma" in literature compared to our experience. Evidence acquisition We searched the PubMed/Medline database all clinical series reporting 5-ALA guided-surgery in not malignant glioma. We reviewed all data also showing our experience. Evidence synthesis Fluorescence guided surgery with 5-ALA might be helpful not only in high-grade glioma but also in other brain tumor especially in Low grade glioma with a suspect of anaplastic spot, meningioma with bone invasion or parenchymal infiltration, ependymoma, lymphoma and pediatric tumors. Conclusions Due to the relatively few number or clinical studies, prospective clinical trials are needed to increase the overall level of evidence concerning the usage of 5-ALA in CNS tumors different from high-grade glioma. Furthermore, a greater us of new tools such as, spectroscopy or confocal microscope or the use of combination of other fluorescence could make more effective this technique.

Premesse. La crescente complessita dei sistemi sanitari, accompagnata dalle numerose innovazioni della tecnologia biomedica, ha contribuito negli ultimi anni a un sovrautilizzo della diagnostica di laboratorio. Il recente Report dell’Institute of Medicine (IOM) Improving Diagnosis in Health Care si occupa anche di Medicina di Laboratorio e conclude che il processo diagnostico richiede sempre piu un approccio di squadra intra- e interprofessionale. E confermato, quindi, che le difficolta teoriche e pratiche della promozione del ruolo dei professionisti del Laboratorio nei diversi sistemi sanitari sono note e dibattute da tempo, mentre gli esempi di modalita strutturate per limitare, d’intesa con i clinici, la richiesta di esami inappropriati, sono pochi.

Background and Importance: Symptomatic vasospasm is a well-known pathology associated with ruptured aneurysms. Nevertheless, this condition is rarely found as a result of skull base tumor removal. Case Presentation: We reported a new case of 40-year-old woman previously treated for a tuberculum and diaphragma sellae meningioma showing symptomatic vasospasm after twelve post-operative days without previously documented sub-arachnoid hemorrhage (SAH). A digital subtraction angiography (DSA) was performed, and a bilateral vasospasm was detected. After subsequent endovascular treatments by intra-arterial infusion of nimodipine, the patient experienced a full recovery. Conclusion: Symptomatic vasospasm after meningioma removal is a challenging and life-threatening condition. Early diagnosis is the key for successful treatment.

Cerebral cavernous angiomas are vascular malformations characterized by large adjacent vessels. Usually, these lesions are smaller than 3 cm, the mean age at presentation occurs between 20 and 40 years, and the neuroradiological findings are well described, especially for magnetic resonance imaging, where the “popcorn balls” appearance is due to the presence of locules containing blood. Among these, the giant cavernous angiomas are very rare, particularly in adults. We collected clinical and neuroradiological data from clinical file and hospital diagnostic archive. A comprehensive review of similar cases was performed. We describe the clinical, diagnostic, and surgical management of a giant cerebral cavernous angioma located in the left deep frontal lobe mimicking a high-grade glioma in an adult Chinese patient. Giant cerebral cavernous angioma may be misdiagnosed and should be considered as differential diagnosis.

Background When fashioning a retrosigmoid craniotomy, precise placement of the initial burr hole is crucial to avoid iatrogenic sinusal injury and to facilitate a corridor that allows for minimal cerebellar retraction. Methods 3D CT reconstructions of 16 cadaveric sides were used to identify and measure three discrete anatomical points. These three points and distances between them were plotted onto the surface of the skull using a digital caliper to identify the optimal burr hole location. This technique was subsequently applied in 20 clinical cases. Results Optimal burr hole placement was achieved in 87.5% of specimens and, with minor refinement, 100% of clinical cases with no significant increase in operative time. Preoperative planning took an average of 10 minutes. Conclusion This technique for localizing the location of the initial retrosigmoid burr hole is a simple, safe, reliable, rapid, and inexpensive solution for surgeons who do not have regular access to neuronavigation.

Background & Importance: Our study was performed based on the first case, reported in English, of a patient with three contemporary lesions, an extra-axial malformation and two vascular ones. Case Presentation: A 62-year-old man referred to our clinic due to right hand tremor associated to a slowing of idea-forming function and movements. The neuroradiological evidence showed a right fronto-temporal meningioma with the contemporary presence of an arteriovenous malformation (AVM) and of an aneurysm. The neuroradiological finding showed, also, a presumably “flow-related” right carotid-ophthalmic aneurysm with two millimeters in size. We performed the meningioma excision by the usage of cavitron ultrasonic surgical aspirator (CUSA), after the isolation of the sylvian fissure with the microdoppler and the removal of the AVM by the Hashimoto technique. Considering the very small size of the aneurysm, we decided to leave it in site. Conclusion: The post-operative examination showed a complete removal of the lesions, meningioma and AVM. We performed an exhaustive review of the current literature, and the result encompassed only another case, written in Japanese, about the contemporary presence of these three lesions.

Background Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naive HIV-1-infected patients with pre-therapy viral load (VL) >500,000 copies/ml was assessed after 12 months of treatment according to initial drug-class regimens. Methods An observational multicentre retrospective study was performed. VS was defined as the first VL + T-lymphocytes from treatment start. Survival analysis was used to estimate the probability and predictors of VS and IR by 12 months of therapy. Results 428 HIV-1-infected patients were analysed. Patients were grouped according to the different first-line drug-classes used: a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs; NNRTI-group; n=105 [24.5%]); a protease inhibitor (PI) plus two NRTIs (PI-group; n=260 [60.8%]); a four-drug regimen containing a PI-regimen plus an integrase inhibitor (PI+INI-group; n=63 [14.7%]). Patients in the PI-group showed the lowest probability of VS (PI-group: 72.4%; NNRTI-group: 75.5%; PI+INI-group: 81.0%; PConclusions In this multicentre retrospective study, patients with viraemia >500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

Objective Our previous studies on CD4-guided therapy interruption (TI) showed that the durations of the first and second TIs were similar if antiretroviral therapy (ART) was resumed at a level of the CD4 cell count similar to or higher than the nadir CD4 T-cell count. Therefore, in a strategy of repeated CD4-guided TI, it is important to know which factors predict the time for the CD4 T-cell count to return to nadir (TRN). Methods From a cohort of 125 patients who interrupted ART, 92 patients who reached a CD4 T-cell count similar to the nadir count were included in the study. Results The median TRN was 12.3 months. In the multivariate analysis, younger age (P=0.011), lower pre-ART HIV RNA (P=0.022) and female gender (P=0.045) were associated with a longer TRN. After TI there were 11 clinical events in the group of patients whose nadir CD4 count was >200 cells/μL. Most of these events occurred when the TI was prolonged beyond the TRN. Conclusions The factors predicting the TRN were age, HIV RNA pre-ART and gender. Resumption of therapy at a CD4 cell count similar to the nadir CD4 count appears to protect against the development of clinical events. Given the observational nature of this study, no conclusions can be drawn regarding the possible application of TI in clinical practice.

Objectives: To evaluate the safety of treatment interruption (Tl) guided by CD4+ count in HIV-infected patients followed-up prospectively. Methods: Patients on HAART with a CD4+ cell count >500 cells/mm 3 discontinued therapy with instructions to start therapy again before their CD4+ count dropped below 200 cells/mm 3 . Results: We report data on 112 HIV-infected patients. The median follow-up after starting the first Tl was 34.7 months (IQR: 23.1-43.8). The median duration of the first Tl was 12 months (IQR: 5.2-25). In the multivariate analysis the factor which most strongly correlated with the duration of the first Tl was the CD4+ cell count at the end of the Tl. Among the 34 patients who had completed a second Tl, the duration of the two periods of interruption was similar if the treatment was recommenced at the end of the first Tl at a CD4+ count higher than the nadir count. Conclusions: The strategy of Tl is safe if the criteria for restarting therapy are applied correctly. The factor with the greatest influence on the duration of the first Tl is the number of CD4+ cells at the end of the Tl.

The aim of this meta-analysis study was to evaluate the relative risk of death or AIDS-defining events associated to CD4+ guided treatment interruption in patients with chronic HIV infection. A search was conducted using PubMed and Cochrane Library; key words for PubMed were: "antiretroviral therapy and interrupt*" in the full papers from January 1, 2000 up to and including December 31, 2007. To limit the publication bias, clinical trials performed on the topic of the meta-analysis were searched also on http://www.clinicaltrial.gov. Inclusion criteria of studies were: starting a CD4+ guided interruption of HAART in HIV chronically infected patients with CD4+ cell count350 cells/mm3, age13 years old, and absence of concomitant use of immunomodulatory drugs. Using a conservative approach, to be included in the meta-analysis, studies had to have a follow up period100 person years to minimize the bias of a too short observation time. The studies were classified into two categories: randomized clinical trial (one arm stops therapy and other arms continues HAART) and cohort studies. For each study measures of effect (hazard ratio or incidence rate ratio) were reported, when available, uncorrected and corrected for potential confounders. Publication bias was assessed graphically through funnel plot. Pooled relative risk and pooled risk difference were calculated by use of a random effects model following the DerSimonian-Laird method. Observational studies were considered separately and the incidence of primary endpoint was evaluated in each study and the cumulative incidence was calculated. Of the 555 full papers found, all abstracts were screened and 58 full text articles for potential inclusion were retrieved and 18 were retained (seven randomized clinical trials and 11 observational studies). In randomized clinical trials, the meta-analysis showed that the pooled relative risk of AIDS-defining event or mortality was 2.50 (95% CI: 1.87-3.34; p0.001); the pooled risk difference of AIDS-defining event or mortality was 0.02 (95% CI: capital ER, Cyrillic0.01-0.05; p = 0.168). The respective values corrected for latest CD4+ value were 1.77 (95% CI: 1.29-2.42; p0.001) and 0.01 (95% CI: capital ER, Cyrillic0.01-0.02; p = 0.37). The pooled relative risk of death was 1.8 (95% CI: 1.18-2.77; p = 0.007), and the corresponding pooled risk difference was 0.01 (95% CI: 0.001-0.012; p = 0.03). The risk of death resulted to have increased in patients that interrupted treatment; the corresponding value of risk difference was significant, although it was low (one extra death per 100 person years). Considering that a separate analysis corrected for the latest CD4+ value was not feasible for this endpoint, and that mortality rates in HIV-infected patients are inversely correlated with the CD4+ count, the value reported is extremely conservative. In cohort studies, the cumulative incidence of deaths or AIDS-defining events in the five studies with follow-up100 person years, was 0.77 (95% CI: 0.37-1.42 events per 100 person years), ranging in different studies from 0 to 3.2 events per 100 person years. This meta-analysis suggests that in patients undergoing a treatment interruption, there is an increased risk of developing AIDS or death, and that this risk is decreased if a relatively high CD4+ threshold is chosen to reinitiate the treatment, while the risk difference does not reach statistical significance.

To evaluate the safety of treatment interruption guided by CD4+ cell count in HIV-infected patients followed up prospectively.Patients on highly active antiretroviral therapy with CD4+ cell counts500 x 10(6) cells/l discontinued therapy with instructions to start therapy again before their CD4+ count dropped below 200 x 10(6) cells/l. Any patients who resumed therapy would be eligible to interrupt treatment again once their CD4+ cell count increased above 500 x 10(6) cells/l.Data on 71 HIV infected patients is reported. Their median nadir CD4+ cell count before antiretroviral treatment was 352 x 10(6) cells/l [interquartile range (IQR), 294-445 x 10(6) cells/l]. The median CD4+ cell count at the time of first interruption was 790 x 10(6) cells/l (IQR, 657-1041 x 10(6) cells/l). The median follow-up after starting the first treatment interruption was 28.3 months (IQR, 21.4-37.0 months). During the follow-up 49 patients restarted therapy and 22 patients remain off therapy; 24 patients have interrupted therapy twice, nine patients have interrupted therapy three times and six patients four times. No AIDS-defining illnesses occurred during the follow-up. The median duration of the first interruption was 15 months (IQR, 6-26 months). The overall reduction of time on therapy was 71.1%. The duration of the first interruption and the reduction of time on therapy were related to nadir CD4+ cell count. The patients who resumed HAART rapidly regained CD4+ cells and achieved viral suppression.If carefully monitored, treatment interruptions guided by CD4+ cell count in patients with an initially high CD4+ cell counts are clinically safe, decrease exposure to the drugs and do not reduce the efficacy of therapy when this is re-started.

Assessing virological response of four-drugs antiretroviral regimen that include raltegravir (RAL) in naïve patients with high viral load (500,000 copies/mL) selected from a multicentre Italian database.Naïve patients with HIV RNA500,000 copies/mL, who began standard antiretroviral regimens either based on non-nucleoside reverse transcriptase inhibitors (NNRTI) or boosted-PI (PI/r), or a standard regimen plus RAL between 2008 and 2013 were analyzed. Observation was censored at 12 months and the percentage of patients who achieved a viral load below the limit of detection (BLD) was calculated. Virological failure was defined as two consecutive viral loads40 copies/mL.Overall, 179 patients were included (13% with primary HIV infection (PHI), and 42.5% with AIDS diagnosis). Of them, 156 started standard three-drugs antiretroviral regimen (75.6% PI/r-based, 24.4% NNRTI-based. Among patients with PHI, 23 patients (12.8%), 6 (25%) started a four-drugs antiretroviral regimen containing both RAL and PI/r. Patients' characteristics were as follows: males 74%, median age 42 years (IQR 35-51), sexually transmission 75.1%, median CD4 count 156 cells/µL (IQR 47-368) and median HIV-RNA 6.1 log10 copies/mL (IQR 5.8-6.4). 91 of 179 patients (50.8%) reached BLD viral load during the twelve months of observation. Three patients (1.7%) who began regimens PI/r-based with three-drugs had virological rebound after reaching BLD viral load. By use of survival analysis, we show that those patients who added RAL to the standard regimen have reached the primary end point faster (mean 8.4 months (95% CI 7.2-9.6) vs 11.4 (95% CI 11.0-11.8) in PI group and 10.3 (95% CI 9.4-11.1) in NNRTI group; p0.001, Figure 1). In the adjusted analysis, the choice of a standard regimen versus a four-drugs regimen was driven only by higher baseline viral load (OR. 9.05; 95% CI 2.41-37.41; p=0.001).Only half of the naïve patients who began antiretroviral therapy having500,000 copies/mL HIV-RNA had virological success at 12 months. The success was reached faster using the RAL-containing four-drugs regimen, suggesting that strengthening the initial regimen could be an option in patients with very high viral load to improve virological response. Probability of HIV viral load below the limit of detection in naïve HIV-1 patients with viral loads500,000 copies/mL treated with a 4-drugs regimen containing raltegravir versus standard therapy with PI/ or NNRTI.

Three kinds of stainless steel have been analyzed: AISI 304 ordinary plane sheets, AISI 316 L cold‐pressed corrugated sheets, and AISI 316 LN rolled‐up and machined plates (the last two materials employed for the vacuum vessel of the Frascati Tokamak FT). Their surfaces were subjected to two different chemical cleaning treatments: one of them based on a detergent, alkaline bath and the other on a brightening, acid bath. Both of these treatments were followed by baking in vacuo to 350°C or more. As a common result outgassing rates below 10−12 Torr l s−1 cm−2 at room temperature were in any case obtained. Nevertheless, the residual content of nonmetallic impurities (mainly oxygen and carbon) found by the depth profile AES analysis significantly varied from sample to sample, depending on the different kind of material (and according to the different chemical process undergone. The adopted brightening bath proved very effective in relieving all the treated surfaces from every kind of impurities, including oxides (oxygen was reduced to the minimum possible amount). The alkaline bath proved more effective in removing carbon, which in any case was reduced to a very small amount. Both the AISI 316 materials used for the vacuum vessel of the FT device showed, after either of the mentioned treatments, fewer nonmetallic impurities than the most common AISI 304 sheets.