The Interplay Between Host Genetic Variation, Viral Replication, and Microbial Translocation in Untreated HIV-Infected Individuals

Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid-binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infectio

Bleeding risk of cerebral cavernous malformations in patients on β-blocker medication: a cohort study.

OBJECTIVE Cerebral cavernous malformations (CCMs) are frequently diagnosed vascular malformations of the brain. Although most CCMs are asymptomatic, some can be responsible for intracerebral hemorrhage or seizures. In selected cases, microsurgical resection is the preferred treatment option. Treatment with the unselective β-blocker propranolol has been presumed to stabilize and eventually lead to CCM size regression in a limited number of published case series; however, the underlying mechanism and evidence for this effect remain unclear. The aim of this study was to investigate the risk for CCM-related hemorrhage in patients on long-term β-blocker medication. METHODS A single-center database containing data on patients harboring CCMs was retrospectively interrogated for a time period of 35 years. The database included information about hemorrhage and antihypertensive medication. Descriptive and survival analyses were performed, focusing on the risk of hemorrhage at presentation and during follow-up (first or subsequent hemorrhage) in patients on long-term β-blocker medication versus those who were not. Follow-up was censored at the first occurrence of new hemorrhage, surgery, or the last clinical review. For purposes of this analysis, the β-blocker group was divided into the following main subgroups: any β-blocker, β1-selective β-blocker, and any unselective β-blocker. RESULTS Of 542 CCMs among 408 patients, 81 (14.9%) were under treatment with any β-blocker; 65 (12%) received β1-selective β-blocker, and 16 (3%) received any unselective β-blocker. One hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the β-blocker groups was associated with a lower risk of hemorrhage at the time of diagnosis in a univariate descriptive analysis (any β-blocker: p = 0.64, β1-selective: p = 0.93, any unselective β-blocker: p = 0.25). Four hundred ninety-six CCMs were followed up after diagnosis and included in the survival analysis, for a total of 1800 lesion-years. Follow-up hemorrhage occurred in 36 (7.3%) CCMs. Neither univariate descriptive nor univariate Cox proportional-hazards regression analysis showed a decreased risk for follow-up hemorrhage under treatment with β-blocker medication (any β-blocker: p = 0.70, HR 1.19, 95% CI 0.49-2.90; β1-selective: p = 0.78, HR 1.15, 95% CI 0.44-3.00; any unselective β-blocker: p = 0.76, HR 1.37, 95% CI 0.19-10.08). Multivariate Cox proportional-hazards regression analysis including brainstem location, hemorrhage at diagnosis, age, and any β-blocker treatment showed no reduced risk for follow-up hemorrhage under any β-blocker treatment (p = 0.53, HR 1.36, 95% CI 0.52-3.56). CONCLUSIONS In this retrospective cohort study, β-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up

Survival and Outcome After Poor-Grade Aneurysmal Subarachnoid Hemorrhage in Elderly Patients.

Background and Purpose- Whether maximal treatment should be offered to elderly patients suffering from poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is controversial. The survival of patients in this subgroup beyond the usual outcome measurements 6 to 12 months after aSAH is unclear. The purpose of this study is to provide survival and outcome data to support clinicians making decisions on treatment for this subgroup of patients. Methods- We performed a retrospective analysis of the Bernese SAH database for poor-grade (World Federation of Neurosurgical Societies grade IV and V) elderly patients (age ≥60 years) suffering from aSAH admitted to our institution from 2005 to 2017. Patients were divided into 3 age groups (60-69, 70-79, and 80-90 years). Survival analysis was performed to estimate mean survival and hazard ratios for death. Binary logarithmic regression was used to estimate the odds ratio for favorable (modified Rankin Scale score of 0-3) and unfavorable (modified Rankin Scale score of 4-6) outcome. Results- Increasing age was associated with an increasing risk of death after aSAH. The hazard ratio increased by 6% per year of age ( P<0.001; hazard ratio, 1.06; 95% CI, 1.03-1.09) and 76% per decade ( P<0.001; hazard ratio, 1.76; 95% CI, 1.35-2.29). Mean survival was 56.3±8 months (patients aged 60-69 years), 31.6±7.6 months (70-79 years), and 7.6±5.8 months (80-90 years). Unfavorable outcomes 6 to 12 months after aSAH were strongly related to older age. The odds ratio increased by 11% per year of age ( P<0.001; odds ratio, 1.11; 95% CI, 1.05-1.18) and 192% per decade ( P<0.001; odds ratio, 2.92; 95% CI, 1.63-5.26). Conclusions- Risk for death and unfavorable outcome increases markedly with older age in elderly patients with poor-grade aSAH. Despite a high initial mortality, treatment resulted in a reasonable proportion of favorable outcomes up to 79 years of age and only a small number of patients who were moderately or severely disabled 6 to 12 months after aSAH. Mean survival and proportion of favorable outcomes decreased markedly in patients older than 80 years

Marriage and partnership integrity after aneurysmal SAH: Small alterations in neurological status matter most.

Common sequelae of subarachnoid hemorrhage (SAH) include somatic and/or cognitive impairment. This can cause emotional stress, social tensions, and difficulties in relationships. To test our hypothesis that more severe somatic and cognitive impairments increased the likelihood of disruption of a relationship after SAH, we assessed the integrity of marriage or partnership status in a well-evaluated subset of SAH patients.; Abbreviations: GOSE: extended Glasgow outcome scale;mRS: modified Rankin scale;SAH: subarachnoid hemorrhage

Tissue fusion, a new opportunity for sutureless bypass surgery

Microsurgical suturing is the standard for cerebral bypass surgery, a technique where temporary occlusion is usually necessary. Non-occlusive techniques such as excimer laser-assisted non-occlusive anastomosis (ELANA) have certainly widened the spectrum of treatment of complex cerebrovascular situations, such as giant cerebral aneurysms, that were otherwise non-treatable. Nevertheless, the reduction of surgical risks while widening the spectrum of indications, such as a prophylactic cerebral bypass, is still a main aim, that we would like to pursue with our sutureless tissue fusion research. The primary concern in sutureless tissue fusion- and especially in tissue fusion of cerebral vessels- is the lack of reproducibility, often caused by variations in the thermal damage of the vessel. This has prevented this novel fusion technique from being applicable in daily surgical use. In this overview, we present three ways to further improve the laser tissue soldering technique.In the first section entitled "Laser Tissue Soldering Using a Biodegradable Polymer," a porous polymer scaffold doped with albumin (BSA) and indocyanine green (ICG) is presented, leading to strong and reproducible tensile strengths in tissue soldering. Histologies and future developments are discussed.In the section "Numerical Simulation for Improvement of Laser Tissue Soldering," a powerful theoretical simulation model is used to calculate temperature distribution during soldering. The goal of this research is to have a tool in hand that allows us to determine laser irradiation parameters that guarantee strong vessel fusion without thermally damaging the inner structures such as the intima and endothelium.In a third section, "Nanoparticles in Laser Tissue Soldering," we demonstrate that nanoparticles can be used to produce a stable and well-defined spatial absorption profile in the scaffold, which is an important step towards increasing the reproducibility. The risks of implanting nanoparticles into a biodegradable scaffold are discussed.Step by step, these developments in sutureless tissue fusion have improved the tensile strength and the reproducibility, and are constantly evolving towards a clinically applicable anastomosis technique

Nimodipine-Induced Blood Pressure Changes Can Predict Delayed Cerebral Ischemia.

Background: Early diagnosis of delayed cerebral ischemia (DCI) in patients after aneurysmal subarachnoid hemorrhage (aSAH) still poses a leading problem in neurointensive care. The aim of this study was to analyze the effect of oral Nimodipine administration on systemic blood pressure in patients with evolving DCI compared to patients without DCI. Methods: Systolic (SBP), mean (MAP), and diastolic (DBP) blood pressures were analyzed at the time of Nimodipine administration and additionally 30, 60, and 120 min thereafter on days 1, 3, and 5 after aSAH. Additionally, the 24 h period preceding DCI and in patients without DCI day 10 after aSAH were analyzed. Statistical analysis was performed for SBP, MAP and DBP at time of Nimodipine administration and for the maximal drop in blood pressure after Nimodipine administration. Results: Thirty patients with aSAH were retrospectively analyzed with 17 patients developing DCI ("DCI") and 13 patients who did not ("Non-DCI"). DCI patients showed a more pronounced rise in MAP and DBP over the examined time period as well as a higher decrease in SBP following Nimodipine administration. A fall of 18 mmHg in SBP after Nimodipine administration showed a sensitivity of 82.4% and specificity of 92.3% for occurrence of DCI. Conclusion: An increase of MAP and DBP after aSAH and a heightened sensitivity to Nimodipine administrations may serve as additional biomarkers for early detection of evolving DCI

Quantitative magnetic resonance angiography as a potential predictor for cerebral hyperperfusion syndrome: a preliminary study.

OBJECTIVE Cerebral hyperperfusion syndrome (CHS) is a rare but devastating complication of carotid endarterectomy (CEA). This study sought to determine whether quantitative hemodynamic assessment using MR angiography can stratify CHS risk. METHODS In this prospective trial, patients with internal carotid artery (ICA) stenosis were randomly selected for pre- and postoperative quantitative phase-contrast MR angiography (QMRA). Assessment was standardized according to a protocol and included Doppler/duplex sonography, MRI, and/or CT angiography and QMRA of the intra- and extracranial supplying arteries of the brain. Clinical and radiological data were analyzed to identify CHS risk factors. RESULTS Twenty-five of 153 patients who underwent CEA for ICA stenosis were randomly selected for pre- and postoperative QMRA. QMRA data showed a 2.2-fold postoperative increase in blood flow in the operated ICA (p < 0.001) and a 1.3-fold increase in the ipsilateral middle cerebral artery (MCA) (p = 0.01). Four patients had clinically manifested CHS. The mean flow increases in the patients with CHS were significantly higher than in the patients without CHS, both in the ICA and MCA (p < 0.001). Female sex and a low preoperative diastolic blood pressure were the clearest clinical risk factors for CHS, whereas the flow differences and absolute postoperative flow values in the ipsilateral ICA and MCA were identified as potential radiological predictors for CHS. CONCLUSIONS Cerebral blood flow in the ipsilateral ICA and MCA as assessed by QMRA significantly increased after CEA. Higher mean flow differences in ICA and MCA were associated with the development of CHS. QMRA might have the potential to become a noninvasive, operator-independent screening tool for identifying patients at risk for CHS