Congenital Cytomegalovirus and Autoimmune Neutropenia: Cause or Coincidence?

BACKGROUND: Congenital cytomegalovirus (CCMV) accounts for high rates of infant morbidity and mortality. Neutropenia is a common finding in CCMV infection, of which the age of presentation overlaps with autoimmune neutropenia (AIN). AIN represents one of the most common forms of chronic neutropenia in childhood. METHODS: A literature search exploring biological associations between CCMV and AIN was conducted: PubMed (MEDLINE), Ovid and Web of Science. We further describe 2 cases of concurrent CCMV and AIN. Both cases were confirmed with the indirect granulocyte immunofluorescence test and alternative etiologies for neutropenia excluded. RESULTS: Our 2 patients represent confirmed cases of AIN in infants with CCMV. One patient demonstrated neutropenia while undergoing treatment with Valganciclovir, while the other was never treated. With interruption of Valganciclovir in infant A, neutrophil counts (ANC) did not improve and upon resumption of treatment ANC remained static. CONCLUSIONS: Further studies examining a possible biologic link between CCMV and AIN are advocated for. We encourage clinicians to actively consider AIN in the differential diagnosis of all infants with CCMV presenting with neutropenia

Real-time computer modeling of weakness following stroke optimizes robotic assistance for movement therapy

This paper describes the development of a novel control system for a robotic arm orthosis for assisting patients in motor training following stroke. The robot allows naturalistic motion of the arm and is as mechanically compliant as a human therapist's arms. This compliance preserves the connection between effort and error that appears essential for motor learning, but presents a challenge: accurately creating desired movements requires that the robot form a model of the patient's weakness, since the robot cannot simply stiffly drive the arm along the desired path. We show here that a standard model-based adaptive controller allows the robot to form such a model of the patient and complete movements accurately. However, we found that the human motor system, when coupled to such an adaptive controller, reduces its own participation, allowing the adaptive controller to take over the performance of the task. This presents a problem for motor training, since active engagement by the patient is important for stimulating neuroplasticity. We show that this problem can be solved by making the controller continuously attempt to reduce its assistance when errors are small. The resulting robot successfully assists stroke patients in moving in desired patterns with very small errors, but also encourages intense participation by the patient. Such robot assistance may optimally provoke neural plasticity, since it intensely engages both descending and ascending motor pathways. © 2007 IEEE

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials

OBJECTIVE: To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates. METHODS: Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic. RESULTS: We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty). CONCLUSIONS: The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate

Inter-Device Agreement of Retinal Nerve Fiber Layer Thickness Measurements Using Spectral Domain Cirrus HD OCT

PURPOSE: To assess the inter-device agreement of peripapillary retinal nerve fiber layer (RNFL) thickness measurements by 2 spectral domain Cirrus HD optical coherence tomography (OCT) devices in healthy Korean subjects. METHODS: Eleven eyes of 11 healthy volunteers were enrolled in the present study. Each eye was scanned with the Optic Disc Cube 200 x 200 scan of 2 Cirrus HD OCT devices for peripapillary RNFL thickness calculation. The inter-device agreements of the 2 Cirrus HD OCTs for average, quadrant, and clock-hour RNFL thickness values were determined with Wilcoxon signed rank test, Friedman test, Cronbach's alpha (alpha), intraclass correlation coefficient (ICC), coefficient of variation (COV), and Bland-Altman plot. RESULTS: The mean age of the participants was 25.82 +/- 3.28 years and all had a 0.00 logarithm of the minimum angle of resolution of best-corrected visual acuity. The signal strengths of scans from the 2 Cirrus HD OCT were not significantly different (p = 0.317). The inter-device agreement of average RNFL thickness was excellent (alpha, 0.940; ICC, 0.945; COV, 2.45 +/- 1.52%). However, the agreement of nasal quadrant RNFL thickness was not very good (alpha, 0.715; ICC, 0.716; COV, 5.72 +/- 4.64%). Additionally, on the Bland-Atman plot, the extent of agreement of the 2 Cirrus HD OCTs for RNFL thickness was variable according to scanned sectors. CONCLUSIONS: The inter-device agreement of 2 spectral domain Cirrus HD OCT devices for peripapillary RNFL thickness measurements was generally excellent but variable according to the scanned area. Thus, physicians should consider this fact before judging a change of RNFL thicknesses if they were measured by different OCT devices.ope

Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

<p>Abstract</p> <p>Background</p> <p>Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O₂) with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-κB) were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin for retinal ganglion cells.</p> <p>Results</p> <p>After 48 hours of hypoxic culture, the LDH assay showed 52.3% cell loss, which was reduced to 25.6% and 30.1% when agmatine and BDNF were administered, respectively. This observed cell loss was due to apoptotic cell death, as established by annexin V and caspase-3 assays. Although total expression of MAPKs and NF-κB was not influenced by hypoxic injury, phosphorylation of these two proteins was increased. Agmatine reduced phosphorylation of JNK and NF-κB, while BDNF suppressed phosphorylation of ERK and p38.</p> <p>Conclusion</p> <p>Our results show that agmatine has neuroprotective effects against hypoxia-induced retinal ganglion cell damage in RGC-5 cells and that its effects may act through the JNK and NF-κB signaling pathways. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce retinal ganglion cell injury related to hypoxia.</p

Lipid levels and major adverse cardiovascular events in patients initiated on statins for primary prevention: an international population-based cohort study protocol

Background : Clinical guidelines recommend specific targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) for primary prevention of cardiovascular disease (CVD). Furthermore, individual variability in lipid response to statin therapy requires assessment of the association in diverse populations. Aim: To assess whether lower concentrations of LDL-C and non-HDL-C are associated with a reduced risk of major adverse cardiovascular events (MACE) in primary prevention of CVD. Design & setting: An international, new-user, cohort study will be undertaken. It will use data from three electronic health record databases from three global regions: Clinical Practice Research Datalink, UK; PREDICT-CVD, New Zealand (NZ); and the Clinical Data and Analysis Reporting System, Hong Kong (HK). Method: New statin users without a history of atherosclerotic CVD, heart failure, or chronic kidney disease, with baseline and follow-up lipid levels will be eligible for inclusion. Patients will be classified according to LDL-C (<1.4, 1.4–1.7, 1.8–2.5, and ≥2.6 mmol/l) and non-HDL-C (<2.2, 2.2–2.5, 2.6–3.3, and ≥3.4 mmol/l) concentrations 24 months after initiating statin therapy. The primary outcome of interest is MACE, defined as the first occurrence of coronary heart disease, stroke, or cardiovascular death. Secondary outcomes include all-cause mortality and the individual components of MACE. Sensitivity analyses will be conducted using lipid levels at 3 and 12 months after starting statin therapy. Conclusion: Results will inform clinicians about the benefits of achieving guideline recommended concentrations of LDL-C for primary prevention of CVD

Short-Term Effects of Ginkgo biloba Extract on Peripapillary Retinal Blood Flow in Normal Tension Glaucoma

PURPOSE: Based on the vascular theory of glaucoma pathogenesis, we wanted to evaluate the effect of Ginkgo biloba extract (GBE) on peripapillary blood flow in patients with normal tension glaucoma (NTG). METHODS: Thirty patients with NTG were randomly placed in the GBE-treated or control groups. The GBE-treated group received 80 mg GBE orally, twice a day for four weeks, and the control group received a placebo twice a day for four weeks. Complete ocular examinations including visual field, Heidelberg retina flowmeter, and systemic examinations were performed on the first study day and on the day treatment was completed. RESULTS: After GBE treatment, the mean blood flow, volume, and velocity increased at almost all points, and there was a statistically significant increase in blood flow at almost all points, in comparison to the placebo. Blood volume significantly increased only in the superior nasal and superior temporal neuroretinal rim areas. GBE also significantly increased blood velocity in areas of the inferior temporal neuroretinal rim and superior temporal peripapillary area. CONCLUSIONS: GBE administration appears to have desirable effect on ocular blood flow in NTG patients.ope

Air-turbine handpiece force vector measurement in clinical procedures

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Development of a standardized in-hospital cardiopulmonary resuscitation set-up

Objective. This study evaluated whether chest compression in a standardized inhospital cardiopulmonary resuscitation (CPR) set-up can be performed as effectively as when the rescuer is kneeling beside the patient lying on the floor. Specifically, the in-hospital test was standardized according to the rescuers’ average knee height. Methods. Experimental intervention (test 1) was a standardized, in-hospital CPR set-up: first, the bed height was fixed at 70 cm. Second, the height difference between the bed and a step stool was set to the average knee height of the CPR team members (45 cm). Control intervention (test 2) was kneeling on floor. Thirty-eight medical doctors on the CPR team each performed 2 minutes of chest compressions in test 1 and 2 in random order (cross-over trial). A Little Anne was used as a simulated patient who had experienced cardiac arrest. Chest compression parameters, such as average depth and rate, were measured using an accelerometer device. Results. In all tests, the average depths were those recommended in the most recent CPR guidelines (50–60 mm); there were no significant differences between Tests 1 and 2 (53.1 ± 4.3 mm vs. 52.6 ± 4.8 mm, respectively; p = 0.398). The average rate in Test 2 (119.1 ± 12.4 numbers/min) was slightly faster than that in Test 1 (116.4 ± 10.2 numbers/ min; p = 0.028). No differences were observed in any other parameters. Conclusions. Chest compression quality in our standardized in-hospital CPR set-up was similar with that performed in a kneeling position on the floor. Trial Registration: Clinical Research Information Service: KCT000159