An Overview of Ovarian Calyx Fluid Proteins of Toxoneuron nigriceps (Viereck) (Hymenoptera: Braconidae): An Integrated Transcriptomic and Proteomic Approach.

The larval stages of the tobacco budworm, Heliothis virescens (Fabricius) (Lepidoptera: Noctuidae), are parasitized by the endophagous parasitoid wasp, Toxoneuron nigriceps (Viereck) (Hymenoptera: Braconidae). During the injections of eggs, this parasitoid wasp also injects into the host body the secretion of the venom gland and the calyx fluid, which contains a polydnavirus (T. nigriceps BracoVirus: TnBV) and the Ovarian calyx fluid Proteins (OPs). The effects of the OPs on the host immune system have recently been described. In particular, it has been demonstrated that the OPs cause hemocytes to undergo a number of changes, such as cellular oxidative stress, actin cytoskeleton modifications, vacuolization, and the inhibition of hemocyte encapsulation capacity, which results in both a loss of hemocyte functionality and cell death. In this study, by using a combined transcriptomic and proteomic analysis, the main components of T. nigriceps ovarian calyx fluid proteins were identified and their possible role in the parasitic syndrome was discussed. This study provides useful information to support the analysis of the function of ovarian calyx fluid proteins, to better understand T. nigriceps parasitization success and for a more thorough understanding of the components of ovarian calyx fluid proteins and their potential function in combination with other parasitoid factors.

How I do it: intradural anterior petrosectomy.

BACKGROUND: The anterior transpetrosal approach (ATPA) is a cranial base approach for addressing upper petroclival or lateral pontine lesions. It is fundamentally an epidural procedure involving the drilling of the petrous apex. However, this approach has significant procedure-related morbidity, and the surgeon must perform a complete petrosectomy, as the intradural structures are not in view during the drilling. For selected cases, a rationale exists for choosing a tailor-made intradural anterior petrosectomy (IAP). METHOD: This article describes the relevant surgical anatomy and the different surgical steps of the IAP. CONCLUSION: IAP represents a feasible alternative to the standard ATPA with the advantage of minimizing the extent of petrous bone removal to the individual need.

Rhino-oropharingeal osteoradionecrotic soft-tissue and bony defect reconstruction with submental artery island flap: a case report.

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.

Surgery of optic-chiasmatic tumors assisted by sodium fluorescein yellow fluorescence and visual evoked potentials monitoring.

BACKGROUND: 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. METHODS: Clinical and Intra-operative data from six surgical procedures on four patients affected by optic-chiasmatic tumours with preoperative visual deficits were retrospectively analysed. RESULTS: 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. CONCLUSIONS: 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.

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak.

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1ß, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann−Whitney or Kruskal−Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53−62); 76% male; median HIV duration of infection, 18 years (15−29); nadir of CD4, 57/mmc (23−100) current CD4 count, 348/mmc (186−565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.

5-aminolevulinic acid and sodium fluorescein in IV ventricle ependymoma surgery: preliminary experience comparing the two techniques.

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.

Are familial colloid cysts of the third ventricle associated with a worse clinical course than sporadic forms?

INTRODUCTION: 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. EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: Fifty-one patients (23 reports, plus our cases) were analyzed from the literature. Familial cases showed a younger age at diagnosis (P=0.02) and fewer asymptomatic cases (P<0.001) compared to non-familial colloid cysts. The odds ratio and relative risk of needing surgery with a positive family history for surgical cyst removal were respectively 17.5 (CI: 1.6-197.4) and 1.9 (CI: 0.71 - 5.1). Screening of other family members identified further colloid cysts in 4% of families. CONCLUSIONS: Familial colloid cysts show a higher percentage of younger and symptomatic patients compared to non-familiar forms. A positive family history for surgical evacuation is a predictor for a similar outcome. This could indicate a predisposition to an earlier formation and faster growth, and the need for a stricter follow-up in asymptomatic patients. If confirmed in the future, this could suggest a review of the criteria for cyst treatment and extend the surgical indication to asymptomatic familial cases.

A Single-Center Experience with the Olympus ORBEYE 4K-3D Exoscope for Microsurgery of Complex Cranial Cases: Technical Nuances and Learning Curve.

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.

Blockage of interleukin-1ß with canakinumab in patients with Covid-19.

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0-30, IQR 4-11). Median PaO2/FiO2 increased from 160 (range 53-409, IQR 122-210) at baseline to 237 (range 72-533, IQR 158-331) at day 7 after treatment with canakinumab (p < 0.0001). Improvement of oxygen support category was observed in 61.4% of cases. Median duration of hospitalization following administration of canakinumab was 6 days (range 0-30, IQR 4-11). At 7 days, 58% of patients had been discharged and 12 (13.6%) had died. Significant differences between baseline and 7 days were observed for absolute lymphocyte counts (mean 0.60 vs 1.11 × 109/L, respectively, p < 0.0001) and C-reactive protein (mean 31.5 vs 5.8 mg/L, respectively, p < 0.0001).Overall survival at 1 month was 79.5% (95% CI 68.7-90.3). Oxygen-support requirements improved and overall mortality was 13.6%. Confirmation of the efficacy of canakinumab for Covid-19 warrants further study in randomized controlled trials.

5-ALA fluorescence on tumors different from malignant gliomas. Review of the literature and our experience.

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.

Preoperative identification of the initial burr hole site in retrosigmoid craniotomies: A teaching and technical note.

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.

Left Deep Frontal Cavernous Angioma Mimicking a Glioma in an Adult Patient.

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.

Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice.

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 <50 copies/ml from treatment start. IR was defined as an increase of at least 150 CD4+ 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%; P<0.0001). By Cox regression, patients in PI+INI and NNRTI-groups showed a higher adjusted hazard ratio (95% CI) of VS compared to those in the PI-group (PI+INI-group: 1.48 [1.08, 2.03]; P=0.014; NNRTI-group: 1.37 [1.06-1.78]; P=0.015). The probability of IR was 76.2%, and was similar among groups. Patients with AIDS showed a lower adjusted hazard ratio (95% CI) of IR compared to non-AIDS presenters (0.70 [0.54, 0.90]; P=0.005). CONCLUSIONS: 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.

Four-drugs regimen containing raltegravir is highly effective in HIV patients starting therapy with >500,000 copies/mL viral load.

INTRODUCTION: 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. METHODS: Naïve patients with HIV RNA>500,000 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 loads>40 copies/mL. RESULTS: 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; p<0.001, 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). CONCLUSIONS: Only half of the naïve patients who began antiretroviral therapy having >500,000 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 loads >500,000 copies/mL treated with a 4-drugs regimen containing raltegravir versus standard therapy with PI/ or NNRTI.

CD4+ guided antiretroviral treatment interruption in HIV infection: a meta-analysis.

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 count > 350 cells/mm3, age > 13 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 period > 100 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; p < 0.001); 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; p < 0.001) 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-up > 100 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.

Safety and factors predicting the duration of first and second treatment interruptions guided by CD4+ cell counts in patients with chronic HIV infection.

OBJECTIVES: To evaluate the safety of treatment interruption (TI) guided by CD4+ count in HIV-infected patients followed-up prospectively. METHODS: Patients on HAART with a CD4+ cell count >500 cells/mm3 discontinued therapy with instructions to start therapy again before their CD4+ count dropped below 200 cells/mm3. RESULTS: We report data on 112 HIV-infected patients. The median follow-up after starting the first TI was 34.7 months (IQR: 23.1-43.8). The median duration of the first TI was 12 months (IQR: 5.2-25). In the multivariate analysis the factor which most strongly correlated with the duration of the first TI was the CD4+ cell count at the end of the TI. Among the 34 patients who had completed a second TI, the duration of the two periods of interruption was similar if the treatment was recommenced at the end of the first TI at a CD4+ count higher than the nadir count. CONCLUSIONS: The strategy of TI is safe if the criteria for restarting therapy are applied correctly. The factor with the greatest influence on the duration of the first TI is the number of CD4+ cells at the end of the TI.