Pitfalls in interpreting red blood cell parameters in elite high-altitude and sea-level athletes:A unique case series

Standard routine hematological measurements are commonly used to investigate differences in blood parameters between high-altitude athletes (HAA) and sea-level athletes (SLA), and to monitor the effect of high-altitude training. In this way, red blood cell (RBC) parameters are usually expressed as relative parameters (concentration) rather than absolute parameters (total amount). In this unique case series of elite HAA and SLA, we describe how different ways of parameter expression can affect the interpretation of blood tests. In a group of 42 elite athletes, relative and absolute RBC parameters were compared between HAA and SLA. Absolute parameters were calculated by multiplying relative values with formula-based estimated blood volume (BV-e). Additionally, in two individual athletes, one HAA and one SLA, absolute parameters were also calculated with blood volume (BV) obtained by measurement with a dilution method (BV-m). In men, HAA had a significantly higher hemoglobin (Hb) concentration (+7.8%; p = 0.001) and total Hb mass per kg body weight (BW) (+12.0%; p = 0.002). When not corrected for BW, HAA had a lower, non-significant, total Hb mass (-7.8%; p = 0.055). In women, no significant differences between HLA and SLA were observed. The two individual athletes showed that, based on BV-m, in the HAA, total Hb mass and total Hb mass per kg BW were respectively 14.1 and 31.0% higher than in the SLA, whereas based on BV-e, in the HAA, total Hb mass was 20.8% lower and total Hb mass per kg BW was only 2.4% higher. Similar inconsistencies were observed for total RBC count. Thus, different ways of parameter expression, and different methods of BV assessment for the calculation of absolute parameter values, influence the interpretation of blood tests in athletes, which may lead to misinterpretation and incorrect conclusions

Secondary infarction in single or in multiple vascular territories: two different entities following subarachnoid hemorrhage?

The pathogenesis of secondary infarctions (SI) after aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. To assess whether SI in single (SSI) or multiple (MSI) vascular territories represent different disease entities, we compared clinical profiles of patients with these patterns of SI. CT/MRI-examinations of 448 patients were reviewed for new infarctions within 28 days after SAH, and categorized into SSI or MSI. Only patients with adequate follow-up imaging excluding any new infarctions were included for analysis (269 patients). Procedure-related infarctions were excluded. Odds ratios (ORs) with corresponding 95% confidence intervals (CI) were calculated for patients with SSI or MSI versus patients without SI to analyze differences in demographic characteristics, vascular risk factors, disease-related characteristics and treatment modalities. Thirty-six patients had SSI, 53 MSI and 180 no SI. ORs in MSI-patients were >1.5 times higher compared with ORs in SSI-patients for multiple vascular risk factors [MSI:5.4 (2.3–13) versus SSI:1.2 (0.5–2.8)], poor clinical condition on admission [MSI:4.6 (2.4–8.9) versus SSI:2.4 (1.1–5.2)], initial loss of consciousness [MSI:2.6 (1.3–5.3) versus SSI:1.1 (0.5–2.3)] and large amounts of intraventricular blood [MSI:2.9 (1.4–5.8) versus SSI:1.5 (0.7–3.2)]. In multivariate analysis ORs remained higher in MSI for presence of multiple vascular risk factors [MSI:1.9 (1.2–2.9) versus SSI:1.1 (0.8–1.7)] and initial loss of consciousness [MSI:3.0 (1.0–8.9) versus SSI:1.6 (0.6–4.0)]. Our findings suggest that SSI and MSI after SAH are not distinct disease entities. MSI was related to the same characteristics as SSI but to a larger extent, specifically to the presence of multiple vascular risk factors, initial loss of consciousness, larger amounts of intraventricular blood, and poor clinical status on admission

Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization

Purpose: Scleritis is a severe inflammatory ocular disorder with unknown pathogenesis. We investigated healthy sclera as well as sclera affected by noninfectious scleritis for differentially expressed proteins using a mass spectrometry approach. Methods: We collected scleral samples of enucleated eyes due to severe noninfectious scleritis (n = 3), and control scleral tissues (n = 5), all exenterated eyes for eyelid carcinomas (n = 4), or choroidal melanoma (n = 1) without scleral invasion. Samples were prepared for the nano liquid-chromatography mass spectrometer (LC-MS), data were analyzed using proteomics software (Scaffold), and is available via ProteomeXchange (identifier PXD038727). Samples were also stained for immuno-histopathological evaluation. Results: Mass spectrometry identified 629 proteins within the healthy and diseased scleral tissues, whereof collagen type XII, VI, and I were the most abundantly expressed protein. Collagen type II-XII was also present. Filaggrin-2, a protein that plays a crucial role in epidermal barrier function, was found upregulated in all scleritis cases. In addition, other epithelial associated proteins were upregulated (such as keratin 33b, 34, and 85, epiplakin, transglutaminase-3, galectin 7, and caspase-14) in scleritis. Further, upregulated proteins involved in regulation of the cytoskeleton (vinculin and myosin 9), and housekeeping proteins were found (elongation factor-2 and cytoplasmic dynein 1) in our study. Upregulation of filaggrin-2 and myosin-9 was confirmed with immunohistochemistry, the latter protein showing co-localization with the endothelial cell marker ETC-related gene (ERG), indicating neovascularization in scleral tissue affected by scleritis. Conclusions: We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis. Further research, ideally including more scleritis cases, is needed to validate our findings.</p

European Stroke Organisation (ESO) Guidelines on Management of Unruptured Intracranial Aneurysms

Unruptured intracranial aneurysms (UIA) occur in around 3% of the population. Important management questions concern if and how to perform preventive UIA occlusion; if, how and when to perform follow up imaging and non-interventional means to reduce the risk of rupture. Using the Standard Operational Procedure of ESO we prepared guidelines according to GRADE methodology. Since no completed randomised trials exist, we used interim analyses of trials, and meta-analyses of observational and case-control studies to provide recommendations to guide UIA management. All recommendations were based on very low evidence. We suggest preventive occlusion if the estimated 5-year rupture risk exceeds the risk of preventive treatment. In general, we cannot recommend endovascular over microsurgical treatment, but suggest flow diverting stents as option only when there are no other low-risk options for UIA repair. To detect UIA recurrence we suggest radiological follow up after occlusion. In patients who are initially observed, we suggest radiological monitoring to detect future UIA growth, smoking cessation, treatment of hypertension, but not treatment with statins or acetylsalicylic acid with the indication to reduce the risk of aneurysm rupture. Additionally, we formulated 15 expert-consensus statements. All experts suggest to assess UIA patients within a multidisciplinary setting (neurosurgery, neuroradiology and neurology) at centres consulting >100 UIA patients per year, to use a shared decision-making process based on the team recommendation and patient preferences, and to repair UIA only in centres performing the proposed treatment in >30 patients with (ruptured or unruptured) aneurysms per year per neurosurgeon or neurointerventionalist. These UIA guidelines provide contemporary recommendations and consensus statement on important aspects of UIA management until more robust data come available.info:eu-repo/semantics/publishedVersio

High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output–Guided Fluid Restriction

Background: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). Methods: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). Results: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P =.012), while preload parameters and consciousness remained stable. Conclusion: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT

Long-Term Follow-Up of Patients with Scleritis After Rituximab Treatment Including B Cell Monitoring

Purpose: We report the long-term effect of rituximab (RTX) in scleritis and determine the value of B-cell monitoring for the prediction of relapses. Methods: We retrospectively studied 10 patients with scleritis, who were treated with RTX. Clinical characteristics were collected, and blood B-cell counts were measured before the start of RTX, and at various time points after treatment. Results:Clinical activity of scleritis decreased after RTX treatment in all patients within a median time of 8 weeks (range 3–13), and all reached remission. The median follow-up was 101 months (range 9–138). Relapses occurred in 6 out of 10 patients. All relapses, where B-cell counts were measured (11 out of 19), were heralded by returning B cells. However, B cells also returned in patients with long-term remissions.Conclusions: RTX is a promising therapeutic option for scleritis. Recurrence of B cells after initial depletion does not always predict relapse of scleritis.</p

Complement C5 contributes to brain injury after subarachnoid hemorrhage

Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n = 229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with outcome. The time course of C5a levels was measured in plasma (n = 31) and CSF (n = 10). In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n = 15 per group). Brain sections from aneurysmal SAH patients showed increased presence of complement components C1q and C3/C3b/iC3B compared to controls. The complement component 5 (C5) SNP correlated with C5a plasma levels and poor disease outcome. Serial measurements in CSF revealed that C5a was > 1400-fold increased 1 day after aneurysmal SAH and then gradually decreased. C5a in plasma was 2-fold increased at days 3–10 after aneurysmal SAH. In the SAH mouse model, we observed a ≈ 40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH

Management decisions on unruptured intracranial aneurysms before and after implementation of the PHASES score

Background: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year risks of rupture based on six easily retrievable patient and aneurysm characteristics. We assessed whether management decisions on UIAs changed after implementation of the PHASES score. Patient and methods: We included all patients with UIAs who were referred to two Dutch tertiary referral centers for aneurysm care in the Netherlands (University Medical Center Utrecht (UMCU) and Leiden University Medical Center (LUMC)) between 2011 and 2017. Analyses were done on an aneurysm level. We calculated the overall proportion of UIAs with a decision to treat before and after PHASES implementation and studied the influence of age and center on post-implementation management changes. Results: We included 623 patients with 803 UIAs. The proportion of UIAs with a decision to treat was 123/360 (34.2%) before and 117/443 (26.4%) after PHASES implementation (absolute risk difference: −7.8%; 95% CI: −14.1 to −1.4). The decision to treat was made at a higher median PHASES score after implementation (7 points (IQR 5;10) pre- versus 8 points (IQR 5;10) post-implementation; p = 0.14). The reduced proportion with a treatment decision after implementation was most pronounced in patients <50 years (−22.3%; 95% CI: −39.2 to −3.4) and was restricted to treatment decisions made at the UMCU (−10.6%; 95% CI: −18.5 to −2.5). Discussion and conclusions: Management of UIAs changed following implementation of the PHASES score, but the impact of PHASES implementation on treatment decisions differed across age subgroups and centers

Lumbar puncture for treating acute hydrocephalus after aneurysmal subarachnoid haemorrhage

Background: External ventricular drainage (EVD) for acute hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH) carries a risk of complications. We studied the proportion of patients in whom EVD can be avoided by treating acute hydrocephalus with ≥1 lumbar punctures (LP). Methods: From a prospectively collected database, we retrieved data on all aSAH patients admitted between 2007 and 2017 who developed acute hydrocephalus (i.e. neurological deterioration and ventricular enlargement <72 h after aSAH). Our regime is to consider LP as initial treatment. We calculated the proportions of patients (with corresponding 95% confidence interval (CI)) who improved after the initial LP and the extent of clinical improvement, the proportions of patients who were treated with only ≥1 LP(s), and those of patients needing continuous external ventricular or external lumbar drainage, or permanent ventriculoperitoneal or lumboperitoneal drainage. Results: Of 1391 consecutive aSAH patients, 473 (34%) had acute hydrocephalus, of whom 388 (82%) were treated. Of the 86 patients with LP as initial treatment, 70 (81% [95% CI 72–88]) showed initial improvement (with increase in median Glasgow Coma Score from 10 (IQR 7–12) to 12 (IQR 9–14) after initial LP), 39 (45% [95% CI 35–56]) improved with LP only, 41 (48% [95% CI 37–58]) needed continuous drainage and six (7% [95% CI 3–14]) needed permanent drainage. Conclusion: Around half the patients treated with LP for deterioration from acute hydrocephalus after aSAH does not require continuous extraventicular or extralumbar drainage

Unusual exanthema combined with cerebral vasculitis in pneumococcal meningitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bacterial meningitis is a complex, rapidly progressive disease in which neurological injury is caused in part by the causative organism and in part by the host's own inflammatory responses.</p> <p>Case presentation</p> <p>We present the case of a two-year-old Greek girl with pneumococcal meningitis and an atypical curvilinear-like skin eruption, chronologically associated with cerebral vasculitis. A diffusion-weighted MRI scan showed lesions with restricted diffusion, reflecting local areas of immunologically mediated necrotizing vasculitis.</p> <p>Conclusions</p> <p>Atypical presentations of bacterial meningitis may occur, and they can be accompanied by serious unexpected complications.</p