Immediate, Early (6 Weeks) and Delayed Loading (3 Months) of Single, Partial and Full Fixed Implant- Supported Prostheses: Three-year Post- Loading Data From a Multicentre Randomised Controlled Trial

PURPOSE. To compare the clinical outcomes of single, partial and complete fixed im-plant-supported prostheses immediately loaded (within 48 hours), early loaded at 6 we-eks, and conventionally loaded at 3 months (delayed loading). MATERIALS AND METHODS. Fifty-four patients (18 requiring single implants, 18 partial fixed prostheses, and 18 total fixed cross-arch prostheses) were randomised in equal numbers in two private practices to immediate loading (18 patients), early loading (18 patients), and conventional loading (18 patients) according to a parallel group design with three arms. To be immediately or early loaded, implants had to be inserted with a torque superior to 40 Ncm. Implants were initially loaded with provisional prostheses, replaced after 4 months by definitive ones. Outcome measures were prosthesis and implant failu-res, complications and peri-implant marginal bone levels. RESULTS. Two conventionally loaded patients rehabilitated with cross-arch fixed total prostheses dropped-out before 3-year post-loading follow-up. No implant failed. One early-loaded partial prosthesis had to be remade (P = 1.0). Three complications occurred in the immediately loaded group, two in the early-loaded and one in the conventionally loaded group with no statistically significant differences across groups (P = 0.861). Pe-ri-implant marginal bone loss was-0.04 ± 0.85 mm at immediately loaded implants,-0.01 ± 0.55 mm at early-loaded implants and 0.33 ± 0.36 mm at conventional loaded implants with no statistically significant differences between the three loading strategies (P=0.191). CONCLUSIONS. All loading strategies were highly successful, and no differences were observed in terms of implant survival and complications when implants were loaded immediately, early or conventionally

Advancements in the Treatment of Cerebrovascular Complications of Cancer

Purpose of review: To present the new guidelines and therapeutic options regarding cerebrovascular complications of cancer, mainly ischemic stroke, cerebral venous thrombosis (CVT), and leptomeningeal carcinomatosis (LMC). Recent findings: A temporal trend study (2019) revealed that clinicians are still reluctant to apply thrombolysis to cancer patients, although two new studies (2018) reported no increased mortality. Several clinical trials on direct oral anticoagulants (DOACs) showed their superiority or, at least, non-inferiority compared with low molecular weight heparins in the treatment of venous thromboembolism (VTE) (2018–2019). These trials helped in formulating the new guidelines that are being published and the decisions made for cancer-associated thrombosis (CAT) as a whole. A new DOAC antidote was also officially released (US 2018, Europe 2019). Summary: Thrombolysis is safe in a malignancy setting, thus cancer per se should not be considered a contraindication for thrombolysis. Clinical trials assessing the newest DOACs for cancer-associated arterial thrombosis are scarce; however, based on data from VTE studies, the newest DOACs seem to be safe for CAT in patients that are not in high risk of bleeding or suffering from certain malignancies. The treatment should not be ceased after 6 months, but rather continued as long as the cancer remains active. Decompressive craniectomy should maintain its place in patients with CVST in risk of herniation. Last, the future also holds much promise on the role of novel compounds to be used in LMC

Unilateral thalamic infarction presenting as vertical gaze palsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Vertical gaze palsy is a recognized manifestation of midbrain lesions. It rarely is a consequence of unilateral thalamic infarction.</p> <p>Case presentation</p> <p>We report the case of a 48-year-old African-American woman who presented to our facility with vertical gaze palsy and evidence of left medial thalamic infarct on diffusion-weighted imaging without coexisting midbrain ischemia. The etiology of infarct was determined to be small vessel disease after extensive investigation.</p> <p>Conclusions</p> <p>This report suggests a possible role of the thalamus as a vertical gaze control center. Clinicoradiological studies are needed to further define the role of the thalamus in vertical gaze control.</p

Microbleed Prevalence and Burden in Anticoagulant-Associated Intracerebral Bleed

Prior studies suggest an association between Vitamin K antagonists (VKA) and cerebral microbleeds (CMBs); less is known about nonvitamin K oral anticoagulants (NOACs). In this observational study we describe CMB profiles in a multicenter cohort of 89 anticoagulation-related intracerebral hemorrhage (ICH) patients. CMB prevalence was 51% (52% in VKA-ICH, 48% in NOAC-ICH). NOAC-ICH patients had lower median CMB count [2(IQR:1–3) vs. 7(4–11); P \u3c 0.001]; ≥5 CMBs were less prevalent in NOAC-ICH (4% vs. 31%, P = 0.006). This inverse association between NOAC exposure and high CMB count persisted in multivariable logistic regression models adjusting for potential confounders (OR 0.10, 95%CI: 0.01–0.83; P = 0.034)

Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

<p>Abstract</p> <p>Background</p> <p>Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage.</p> <p>Methods</p> <p>We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset.</p> <p>Results</p> <p>Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke.</p> <p>Conclusion</p> <p>Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially in the small-vessel occlusion strokes.</p

Effect of pre-stroke use of ACE inhibitors on ischemic stroke severity

BACKGROUND: Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEI) are effective in prevention of ischemic stroke, as measured by reduced stroke incidence. We aimed to compare stroke severity between stroke patients who were taking ACEI before their stroke onset and those who were not, to examine the effects of pretreatment with ACEI on ischemic stroke severity. METHODS: We retrospectively studied 126 consecutive patients presenting within 24 hours of ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance imaging (DWI). We calculated the NIHSS score at presentation, as the primary measure of clinical stroke severity, and categorized stroke severity as mild (NIHSS [less than or equal to] 7), moderate (NIHSS 8–13) or severe (NIHSS [greater than or equal to] 14). We analyzed demographic data, risk-factor profile, blood pressure (BP) and medications on admissions, and determined stroke mechanism according to TOAST criteria. We also measured the volumes of admission diffusion- and perfusion-weighted (DWI /PWI) magnetic resonance imaging lesions, as a secondary measure of ischemic tissue volume. We compared these variables among patients on ACEI and those who were not. RESULTS: Thirty- three patients (26%) were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5 (range 2–21) among ACEI-treated patients vs. 9 (range 1–36) in non-ACEI patients (p = 0.036). Patients on ACEI prior to their stroke had more mild and less severe strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated patients. However, none of these differences were significant. Predictably, a higher percentage of patients on ACEI had a history of heart failure (p = 0.03). Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant therapy with lipid lowering, other antihypertensives or antithrombotic agents, or admission BP were comparable between the two groups. CONCLUSION: Our results suggest that ACE-inhibitors may reduce the clinical severity of stroke, as measured by NIHSS score. Further, larger-scale, prospective studies areneeded to validate our findings, and to elucidate the mechanism(s) of ACEImediated benefits in patients with ischemic stroke

Fabry disease in children and the effects of enzyme replacement treatment

Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficiency in the activity of the lysosomal enzyme, α-galactosidase A. In affected patients, the enzyme substrate, globotriaosylceramide (Gb3), accumulates in cells of various tissues and organs. Lysosomal accumulation of Gb3 begins in utero, and signs and symptoms of Fabry disease emerge in childhood and adolescence. The earliest presenting symptoms are typically neuropathic pain and gastrointestinal problems, which can have a substantial impact on health-related quality of life. Life-threatening major organ involvement is rare in young patients, but signs of kidney dysfunction (e.g., proteinuria), left ventricular hypertrophy, and stroke have been reported in children. There are two enzyme preparations for therapy: agalsidase alfa and beta. In two clinical trials of enzyme replacement therapy (ERT) with agalsidase alfa, including 37 children, boys demonstrated reductions in plasma Gb3 levels, and both boys and girls reported reductions in neuropathic pain and in the use of neuropathic pain medications. Heart rate variability, which is reduced in boys with Fabry disease, was statistically significantly improved with 6 months of agalsidase alfa treatment. In a single clinical study of agalsidase beta in children (n =16), skin Gb3 deposits and plasma Gb3 levels were reduced in boys. Differences exist in the administration and the safety profile of these two enzyme formulations. Follow-up of these cohorts and additional studies will be necessary to fully evaluate long-term efficacy of ERT in children with Fabry disease

Globotriaosylsphingosine Accumulation and Not Alpha-Galactosidase-A Deficiency Causes Endothelial Dysfunction in Fabry Disease

BACKGROUND: Fabry disease (FD) is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA) resulting in the accumulation of globotriaosylsphingosine (Gb3) in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs) were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients

Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke

Variations in apparent diffusion coefficient of water (ADC) and blood-brain barrier (BBB) permeability after ischemia have been suggested, though the correlation between ADC alterations and BBB opening remains to be studied. We hypothesized that there are correlations between the alteration of ADC and BBB permeability. Rats were subjected to 2 h of transient middle cerebral artery occlusion and studied at 3 and 48 h of reperfusion, which are crucial times of BBB opening. BBB permeability and ADC values were measured by dynamic contrast-enhanced MRI and diffusion-weighted imaging, respectively. Temporal and spatial analyses of the evolution of BBB permeability and ADC alteration in cortical and subcortical regions were conducted along with the correlation between ADC and BBB permeability data. We found significant increases in BBB leakage and reduction in ADC values between 3 and 48 h of reperfusion. We identified three MR tissue signature models: high Ki and low ADC, high Ki and normal ADC, and normal Ki and low ADC. Over time, areas with normal Ki and low ADC transformed into areas with high Ki. We observed a pattern of lesion evolution where the extent of initial ischemic injury reflected by ADC abnormalities determines vascular integrity. Our results suggest that regions with vasogenic edema alone are not likely to develop low ADC by 48 h and may undergo recovery