Hepatitis B virus replication Beck, Juergen; Nassal, Michael
World journal of gastroenterology : WJG,
01/2007, Letnik:
13, Številka:
1
Journal Article
Odprti dostop
Hepadnaviruses, including human hepatitis B virus （HBV）, replicate through reverse transcription of an RNA intermediate, the pregenomic RNA （pgRNA）. Despite this kinship to retroviruses, there are ...fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription： it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, ε, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV （DHBV）, now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the ~ RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.
OBJECTIVE Outcome analysis of comatose patients (Hunt and Hess Grade V) after subarachnoid hemorrhage (SAH) is still lacking. The aims of this study were to analyze the outcome of Hunt and Hess Grade ...V SAH and to compare outcomes in the current period with those of the pre-International Subarachnoid Aneurysm Trial (ISAT) era as well as with published data from trials of decompressive craniectomy (DC) for middle cerebral artery (MCA) infarction. METHODS The authors analyzed cases of Hunt and Hess Grade V SAH from 1980-1995 (referred to in this study as the earlier period) and 2005-2014 (current period) and compared the results for the 2 periods. The outcomes of 257 cases were analyzed and stratified on the basis of modified Rankin Scale (mRS) scores obtained 6 months after SAH. Outcomes were dichotomized as favorable (mRS score of 0-2) or unfavorable (mRS score of 3-6). Data and number needed to treat (NNT) were also compared with the results of decompressive craniectomy (DC) trials for middle cerebral artery (MCA) infarctions. RESULTS Early aneurysm treatment within 72 hours occurred significantly more often in the current period (in 67% of cases vs 22% in earlier period). In the earlier period, patients had a significantly higher 30-day mortality rate (83% vs 39% in the current period) and 6-month mortality rate (94% vs 49%), and no patient (0%) had a favorable outcome, compared with 23% overall in the current period (p < 0.01, OR 32), or 29.5% of patients whose aneurysms were treated (p < 0.01, OR 219). Cerebral infarctions occurred in up to 65% of the treated patients in the current period. Comparison with data from DC MCA trials showed that the NNTs were significantly lower in the current period with 2 for survival and 3 for mRS score of 0-3 (vs 3 and 7, respectively, for the DC MCA trials). CONCLUSIONS Early and aggressive treatment resulted in a significant improvement in survival rate (NNT = 2) and favorable outcome (NNT = 3 for mRS score of 0-3) for comatose patients with Hunt and Hess Grade V SAH compared with the earlier period. Independent predictors for favorable outcome were younger age and bilateral intact corneal reflexes. Despite a high rate of cerebral infarction (65%) in the current period, 29.5% of the patients who received treatment for their aneurysms during the current era (2005-2014) had a favorable outcome. However, careful individual decision making is essential in these cases.
Health-related quality of life (HRQoL) assessment is becoming increasingly important in neurosurgery following the trend toward patient-centered care, especially in the context of skull base ...diseases. The current study evaluates the systematic assessment of HRQoL using digital patient-reported outcome measures (PROMs) in a tertiary care center specialized in skull base diseases. The methodology and feasibility to conduct digital PROMs using both generic and disease-specific questionnaires were investigated. Infrastructural and patient-specific factors affecting participation and response rates were analyzed. Since August 2020, 158 digital PROMs were implemented in skull base patients presenting for specialized outpatient consultations. Reduced personnel capacity led to significantly fewer PROMs being conducted during the second versus (vs.) the first year after introduction (mean: 0.77 vs. 2.47 per consultation day,
= 0.0002). The mean age of patients not completing vs. those completing long-term assessments was significantly higher (59.90 vs. 54.11 years,
= 0.0136). Follow-up response rates tended to be increased with recent surgery rather than with the wait-and-scan strategy. Our strategy of conducting digital PROMs appears suitable for assessing HRQoL in skull base diseases. The availability of medical personnel for implementation and supervision was essential. Response rates during follow-up tended to be higher both with younger age and after recent surgery.
Petroclival meningioma (PCM) remains a major neurosurgical challenge. There are still controversial strategic treatment concepts about surgical approach, the extent of resection, and postoperative ...radiotherapy. We aimed to evaluate prognostic factors influencing the progression-free survival (PFS) rates of PCM, with a particular focus on the retrosigmoidal approach, the role of the extent of resection, and postoperative radiotherapy.
Eighty-nine patients with complete follow-up data were included. All patients were operated on
a retrosigmoidal approach, of whom 19 underwent gross total resection (GTR) and 70 underwent subtotal resection (STR). In the subgroups of tumors with infiltration of the cavernous sinus, 41 patients received near total resection (NTR) and 24 STR. Thirty-one patients received postoperative radiotherapy of the residual tumor and 58 were treated with surgery alone. Kaplan-Meier analyses and Cox regression were used to identify significant factors associated with treatment.
GTR (
=0.0107) and postoperative radiotherapy (
=0.014) were associated with significantly improved PFS. Even the subgroup analysis of extended PCM with infiltration of the cavernous sinus (CS) showed an advantage for PFS after near total resection (NTR) (
=0.0017). The additional radiotherapy of the residual tumor in the CS in this subgroup also showed a beneficial effect on PFS (
=0.012).
The extension of surgical resection remains the most important prognostic factor in relation to oncological outcomes. However, the GTR of extended PCM with infiltration of the CS is associated with significant neurological morbidity and requires additional adjuvant therapy concepts. Postoperative radiotherapy is an important element in the treatment of the residual tumor after surgery.
Recent studies have demonstrated that the improved prognosis derived from resection of gliomas largely depends on the extent and quality of the resection, making maximum but safe resection the ...ultimate goal. Simultaneously, technical innovations and refined neurosurgical methods have rapidly improved efficacy and safety. Because gliomas derive from intrinsic brain cells, they often cannot be visually distinguished from the surrounding brain tissue during surgery. In order to appreciate the full extent of their solid compartment, various technologies have recently been introduced. However, radical resection of infiltrative glioma puts neurological function at risk, with potential detrimental consequences for patients' survival and quality of life. The allocation of various neurological functions within the brain varies in each patient and may undergo additional changes in the presence of a tumour (brain plasticity), making intra-operative localisation of eloquent areas mandatory for preservation of essential brain functions. Combining methods that visually distinguish tumour tissue and detect tissues responsible for critical functions now enables resection of tumours in brain regions that were previously considered off-limits, and benefits patients by enabling a more radical resection, while simultaneously lowering the risk of neurological deficits. Here we review recent and expected developments in microsurgery for glioma and their respective benefits.
Graves’ orbitopathy (GO) leads to increased orbital tissue and causes symptoms such as exophthalmos, functional complaints, or dysthyroid optic neuropathy. Different GO types with fat and/or muscle ...enlargement were identified, and increased muscle appears to particularly influence visual status and treatment response. The current study examines visual parameters dependent on orbital muscle volume fraction in a surgically treated GO cohort. After volumetric analysis of the preoperative orbital content, 83 orbits in 47 patients were categorized into predefined groups (increased or not-increased muscle fraction). All cases underwent pterional orbital decompression, and pre- and postoperative visual status was retrospectively analyzed. Forty-one orbits revealed increased and 42 orbits revealed not-increased muscle volume (mean fraction 29.63% versus (vs.) 15.60%). The preoperative visual acuity (VA) was significantly lower in orbits with increased vs. not-increased muscle volume (mean VA 0.30 vs. 0.53, difference 2.5 lines). After surgery, mean VA improved significantly by 1.7 lines in orbits with increased muscle volume. Not preoperative, but postoperative exophthalmos was significantly lower in orbits with not-increased muscle volume. Increased orbital muscle is associated with significantly reduced VA, but can be remarkably improved by pterional orbital decompression. Therefore, surgical therapy should be considered particularly in decreased VA with orbital muscle enlargement.
Highlights • Women outnumbered men among aSAH patients, especially along increasing age strata (confirmatory finding). • Women had increased global disease severity on admission. • Medical history, ...clinical/radiological severity of aSAH and complications did not differ significantly between genders.
Vasospastic brain infarction is a devastating complication of aneurysmal subarachnoid hemorrhage (SAH). Using a probe for invasive monitoring of brain tissue oxygenation or blood flow is highly focal ...and may miss the site of cerebral vasospasm (CVS). Probe placement is based on the assumption that the spasm will occur either at the dependent vessel territory of the parent artery of the ruptured aneurysm or at the artery exposed to the focal thick blood clot. We investigated the likelihood of a focal monitoring sensor being placed in vasospasm or infarction territory on a hypothetical basis.
From our database we retrospectively selected consecutive SAH patients with angiographically proven (day 7-14) severe CVS (narrowing of vessel lumen >50%). Depending on the aneurysm location we applied a standard protocol of probe placement to detect the most probable site of severe CVS or infarction. We analyzed whether the placement was congruent with existing CVS/infarction.
We analyzed 100 patients after SAH caused by aneurysms located in the following locations: MCA (n = 14), ICA (n = 30), A1CA (n = 4), AcoA or A2CA (n = 33), and VBA (n = 19). Sensor location corresponded with CVS territory in 93% of MCA, 87% of ICA, 76% of AcoA or A2CA, but only 50% of A1CA and 42% of VBA aneurysms. The focal probe was located inside the infarction territory in 95% of ICA, 89% of MCA, 78% of ACoA or A2CA, 50% of A1CA and 23% of VBA aneurysms.
The probability that a single focal probe will be situated in the territory of severe CVS and infarction varies. It seems to be reasonably accurate for MCA and ICA aneurysms, but not for ACA or VBA aneurysms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Proton magnetic resonance spectroscopy (1H-MRS) delivers information about the non-invasive metabolic landscape of brain pathologies. 1H-MRS is used in clinical setting in addition to MRI for ...diagnostic, prognostic and treatment response assessments, but the use of this radiological tool is not entirely widespread. The importance of developing automated analysis tools for 1H-MRS lies in the possibility of a straightforward application and simplified interpretation of metabolic and genetic data that allow for incorporation into the daily practice of a broad audience. Here, we report a prospective clinical imaging trial (DRKS00019855) which aimed to develop a novel MR-spectroscopy-based algorithm for in-depth characterization of brain lesions and prediction of molecular traits. Dimensional reduction of metabolic profiles demonstrated distinct patterns throughout pathologies. We combined a deep autoencoder and multi-layer linear discriminant models for voxel-wise prediction of the molecular profile based on MRS imaging. Molecular subtypes were predicted by an overall accuracy of 91.2% using a classifier score. Our study indicates a first step into combining the metabolic and molecular traits of lesions for advancing the pre-operative diagnostic workup of brain tumors and improve personalized tumor treatment.
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