Study of combining virtual screening and antiviral treatments of the Sars-CoV-2 (Covid-19).

The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Additionally, general treatments, coronavirus-specific treatments, and antiviral treatments useful in fighting COVID-19 are addressed. This review sets out to shed light on the SARS-CoV-2 and host receptor recognition, a crucial factor for successful virus infection and taking immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein of SARS-CoV-2. A variety of improved or new approaches also have been developed. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection. Moreover, the genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three-dimensional structure of the Main protease (Mpro) is available. The reported structure of the target Mpro was described in this review to identify potential drugs for COVID-19 using virtual high throughput screening.

Hepatitis C cure with antiviral therapy--benefits beyond the liver.

Liver disease is the major complication of chronic HCV infection. However, extrahepatic complications are common (50-75%), including mixed cryoglobulinaemia and B-cell lymphomas. Given that chronic hepatitis C has become curable using expensive oral direct-acting antivirals (DAAs), it seems worth revisiting the whole spectrum and burden of disease in HCV carriers.Herein, we update the most clinically significant medical complications associated with chronic hepatitis C and the evidence of benefits that would derive from a wide use of curative DAA therapies.Chronic HCV infection is associated with a broad spectrum of clinical conditions, including distinct rheumatic disorders (polyarthritis, sicca syndrome), lymphoproliferative conditions (mixed cryoglobulinaemia, monoclonal gammapathies and B-cell lymphomas) and damage at other organs due to persistent systemic inflammation, leading to renal, bone, neurological and/or cardiovascular disease. Eradication of HCV with DAAs is associated with amelioration and/or resolution of most liver-related and extrahepatic complications. Ultimately, gains in quality of life and survival favour treating everyone with hepatitis C regardless of liver fibrosis stage.

Emerging challenges in managing hepatitis B in HIV patients.

Roughly 10 % of HIV-positive individuals worldwide have concomitant chronic hepatitis B virus (HBV) infection, with large differences between geographical regions and/or risk groups. Hepatitis B is a preventable infection with vaccines. However, it cannot be eradicated once acquired, resembling HIV and in contrast with HCV. In developed countries, hepatitis B exhibits particular features in the HIV population. First, HBV infection is less frequently misdiagnosed than in the general population. Second, nucleos(t)ide analogs active against HBV are widely used as part of antiretroviral combinations and are taken by most HIV patients. Lastly, as the HIV population ages given the success of antiretroviral therapy, non-AIDS co-morbidities are becoming a major cause of disease, for which specific drugs are required, increasing the risk of interactions and hepatotoxicity. Furthermore, concern on HBV reactivation is rising as immunosuppressive drug therapies are increasingly been used for cancers and other non-malignant conditions. In this scenario, new challenges are emerging in the management of hepatitis B in HIV-positive individuals. Among them, major interest is focused on failures to suppress HBV replication, HBV breakthroughs and reactivations, the meaning of isolated anti-HBc, screening for liver cancer, and the complexity arising when hepatitis viruses C and/or D are additionally present. This review will focus on these challenges and the major advances in HBV coinfection in HIV.

Drug interactions with new hepatitis C oral drugs.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection has recently become a curable disease with antiviral therapy. The knowledge of drug interactions using direct-acting antivirals (DAA) may permit maximizing antiviral efficacy and avoiding drug-related toxicities. Ageing in the chronic hepatitis C population, along with added co-morbidities that require other medications, has increased the attention on drug interactions using DAA. AREAS COVERED: This review provides an update of the most clinically significant pharmacokinetic and pharmacodynamic drug interactions occurring between currently available DAA and other medications. The review also revisits how drug interactions with DAA can be prevented and managed. EXPERT OPINION: Interactions between DAA and other drugs are frequent in clinical practice. The most frequent drug interactions modify drug metabolism by inducing or inhibiting the cytochrome P450, leading to abnormal drug exposures. Through this mechanism HCV protease inhibitors, especially when co-formulated with ritonavir as pharmacoenhancer, and non-nucleoside HCV polymerase inhibitors interact with other medications. In contrast, NS5B nucleos(t)ide analog inhibitors (i.e., sofosbuvir) and some HCV NS5A inhibitors (i.e., ledipasvir), which do not or only marginally affect CYP450, are relatively free of significant pharmacokinetic interactions. However, exposure to HCV nucleos(t)ide analogs may be influenced by induction/inhibition of drug transporters (i.e., P-glycoprotein) as well as by pharmacodynamic interference with other nucleos(t)ide analogs used as antivirals or cancer drugs. Drug interactions for some NS5A inhibitors (i.e., daclatasvir) are generally moderate and can be managed with dose adjustments.

Role of IL28-B polymorphisms in the treatment of chronic hepatitis B HBeAg-negative patients with peginterferon.

Interleukin (IL)28-B polymorphism has been related to interferon response in the treatment of hepatitis C, but its role in chronic hepatitis B (CHB) therapy is still poorly understood. We aimed to investigate the effect of IL28-B polymorphisms in the treatment with pegylated-interferon (PEG-IFN) of patients with CHB. We retrospectively analyzed 190 patients with chronic hepatitis B e antigen (HBeAg) negative, genotype A (22%), B (12%), C (10%), D (33%), E (20%), treated with PEG-IFN alfa-2a for 48weeks; genotype analysis was performed for IL28-B polymorphisms rs12979860, rs8099917 and rs12980275 according to virological, serological and biochemical response. During 2years of follow-up 12 patients (6.3%) cleared hepatitis B surface antigen (HBsAg) with seroconversion, 40 (21%) obtained a negative viral load and 104 (54.7%) gained a biochemical response. We found a difference of distribution of rs12979860 CC genotype among different ethnicity (p=0.013). Rs12979860 CC genotype was significantly associated with serological and virological response (p<0.001); rs8099917 TT and rs12980275 AA genotypes were mostly related with virological response (p<0.001). In multivariate logistic analysis rs12979860 CC was predictive of virological response (OR=4.290; CI=1.589-11.580, p=0.004) and serological response (OR=10.129; CI=2.440-42.044; p<0.001). Rs8099917 TT was predictive only of virological response (OR=3.746, CI=1.235-11.355; p=0.020). The E genotype was a negative predictive factor of virological response (OR=0.057; CI=0.014-0.238; p<0.001). IL28-B polymorphisms are related to different response in the treatment of CHB HBeAg-negative with PEG-IFN, and the E genotype is a novel negative predictive factor.

Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient. A rare case report and literature review.

Sphingomonas paucimobilis occurs widely both in natural and nosocomial environments, including hospital water systems, respiratory therapy equipment, and laboratory instruments. It is an opportunistic pathogen that rarely causes infections in humans. Among S. paucimobilis nosocomial infections, osteomyelitis is particularly rare. Almost all infections occur in patients with comorbidities such as malignancy, immunosuppressant therapy, diabetes mellitus and acquired immunodeficiency syndrome. We present the first case of Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient and include updated literature concerning infections by this microorganism.

Bone removal with a new ultrasonic bone curette during endoscopic endonasal approach to the sellar-suprasellar area: technical note.

BACKGROUND: Accessing intradural lesions via an extended endoscopic endonasal approach requires a relatively large bony removal over the skull base. OBJECTIVE: We describe the Sonopet ultrasonic bone curette with a new dedicated endonasal hand-piece. MATERIALS AND METHODS: We used this ancillary device in 27 nonconsecutive endonasal procedures for different skull base lesions (18 standard pituitary operations and 9 extended approaches for either meningiomas or craniopharyngiomas). RESULTS: The ultrasonic bone curette with endonasal hand-piece was easy to use and effective during the removal of the bone covering or when close to the carotid and optic prominences, as well as in preserving the integrity of the superior intercavernous sinus. In only 1 case was small tearing of the dura mater observed during the bony removal. No cases of injury to the major neurovascular structures occurred. CONCLUSION: The Sonopet ultrasonic bone curette is a useful tool during endoscopic endonasal skull base surgery.

Endoscopic endonasal transclival approach and retrosigmoid approach to the clival and petroclival regions.

OBJECTIVE: The removal of clival lesions, mainly those located intradurally and with a limited lateral extension, may be challenging because of the lack of a surgical corridor that would allow exposure of the entire lesion surface. In this anatomic study, we explored the clival/petroclival area and the cerebellopontine angle via both the endonasal and retrosigmoid endoscopic routes, aiming to describe the respective degree of exposure and visual limitations. METHODS: Twelve fresh cadaver heads were positioned to simulate a semisitting position, thus enabling the use of both endonasal and retrosigmoid routes, which were explored using a 4-mm rigid endoscope as the sole visualizing tool. RESULTS: The comparison of the 2 endoscopic surgical views (endonasal and retrosigmoid) allowed us to define 3 subregions over the clival area (cranial, middle, and caudal levels) when explored via the endonasal route. The definition of these subregions was based on the identification of some anatomic landmarks (the internal carotid artery from the lacerum to the intradural segment, the abducens nerve, and the hypoglossal canal) that limit the bone opening via the endonasal route and the natural well-established corridors via the retrosigmoid route. CONCLUSION: Different endoscopic surgical corridors can be delineated with the endonasal transclival and retrosigmoid approaches to the clival/petroclival area. Some relevant neurovascular structures may limit the extension of the approach and the view via both routes. The combination of the 2 approaches may improve the visualization in this challenging area.

Use of a thrombin-gelatin haemostatic matrix in endoscopic endonasal extended approaches: technical note.

OBJECTIVE: The management of intradural bleeding during extended endoscopic endonasal surgery is challenging. This technical note describes the use of a biological haemostatic agent which could be useful when other established strategies and materials are not effective. MATERIALS AND METHODS: From January 2004 to January 2008, 65 consecutive patients underwent extended endoscopic endonasal interventions. Of these, 29 procedures required the application of a thrombin-gelatin haemostatic matrix. We reviewed the patients' operative records to determine the source, type of bleeding and haemostatic strategy. RESULTS: We analysed bleedings from the venous sinuses, arteries, tumour bed and internal carotid artery and observed complete haemostasis immediately after application of FloSeal. The matrix was useful for both oozing and focal haemorrhage and effective even for high-flow bleeding. Only bleeding from an internal carotid artery tear required a second application. CONCLUSION: The thrombin-gelatin matrix could represent a valuable tool when other haemostatic strategies are ineffective or suboptimal. It is safe and biocompatible when compared with haemostatic agents currently in use.

Endoscopic transnasal resection of anterior cranial fossa meningiomas.

OBJECT: The extended transnasal approach, a recent surgical advancements for the ventral skull base, allows excellent midline access to and visibility of the anterior cranial fossa, which was previously thought to be approachable only via a transcranial route. The extended transnasal approach allows early decompression of the optic canals, obviates the need for brain retraction, and reduces neurovascular manipulation. METHODS: Between 2004 and 2007, 11 consecutive patients underwent transnasal resection of anterior cranial fossa meningiomas--4 olfactory groove (OGM) and 7 tuberculum sellae (TSM) meningiomas. Age at surgery, sex, symptoms, and imaging studies were reviewed. Tumor size and tumor extension were estimated, and the anteroposterior, vertical, and horizontal diameters were measred on MR images. Medical records, surgical complications, and outcomes of the patients were collected. RESULTS: A gross-total removal of the lesion was achieved in 10 patients (91%), and in 1 patient with a TSM only a near-total (> 90%) resection was possible. Four patients with preoperative visual function defect had a complete recovery, whereas 3 patients experienced a transient worsening of vision, fully recovered within few days. In 3 patients (2 with TSMs and 1 with an OGM), a postoperative CSF leak occurred, requiring a endoscopic surgery for skull base defect repair. Another patient (a case involving a TSM) developed transient diabetes insipidus. The operative time ranged from 6 to 10 hours in the OGM group and from 4.5 to 9 hours in the TSM group. The mean duration of the hospital stay was 13.5 and 10 days in the OGM and TSM groups, respectively. Six patients (3 with OGMs and 3 with TSMs) required a blood transfusion. Surgery-related death occurred in 1 patient with TSM, in whom the tumor was successfully removed. CONCLUSIONS: The technique offers a minimally invasive route to the midline anterior skull base, allowing the surgeon to avoid using brain retraction and reducing manipulation of the large vessels and optic apparatus; hastens postoperative recovery; and improves patient compliance. Further assessment and refinement are required, particularly because of the potential risk of CSF leakage. Other studies and longer follow-up periods are necessary to ascertain the benefits of the technique.

Endoscopic endonasal approach to the ethmoidal planum: anatomic study.

The endoscopic endonasal technique is currently used by otolaryngologists for the management of different extradural lesions located below the ethmoidal planum. The cooperation between ENTs and neurosurgeons has recently pushed the use of such approach also in the removal of some intradural lesions, which has promoted the interest for an anatomic study to identify the anatomical landmarks and the dangerous points during the endoscopic approach to this area. In six fresh cadaver heads, unilateral and bilateral measurements between the main landmarks of the approach were performed by means of an endoscopic endonasal approach. A wide exposure of the midline anterior skull base was realized. The maximum of lateral extension was obtained between the two medial orbital walls, at the middle of the cribriform plate (mean distance 25,33 mm), while the mean distance between the anterior and posterior ethmoidal arteries at the level of the lamina papyracea was 16 mm. The endoscopic endonasal route can be considered a minimally invasive technique to approach the ethmoidal planum. It requires adequate anatomical knowledge and endoscopic skill for its realization. Due to the wide window realizable through this corridor, it could be considered in selected cases for the removal of intradural lesions such as meningiomas or estesioneuroblastomas.

Endoscopic endonasal transsphenoidal surgery. Before scrubbing in: tips and tricks.

BACKGROUND: The interest in endoscopic endonasal transsphenoidal surgery for the treatment of sellar and perisellar lesions is growing as a consequence of the results achieved in the past 10 years and of the interest by patients, endocrinologists, and neurosurgeons. Furthermore, the special ability of the endoscope to offer a wider and detailed view of anatomic structures is a major advantage that increases the attention of neurosurgeons who seek less invasive procedures and better results. Most neurosurgeons performing transsphenoidal surgery, however, are not used to endoscopy, and changing from microsurgical to endoscopic technique can be difficult and even discouraging, often because of difficulties in the initial phase of the procedure. TECHNIQUE: With the purpose of helping minimize some of the difficulties, we describe herein useful tips and tricks that mainly concern familiarization with the endoscopic equipment, details of the transsphenoidal anatomy, and endoscopic skills. We stress the steps and details that we judge most important. CONCLUSION: We believe that by following these recommendations neurosurgeons can overcome, or even avoid, the difficulties frequently encountered transsphenoidal surgery, allowing them to safely and efficiently perform endonasal transsphenoidal endoscopic procedures.