Elevated C1s/C1-INH in serum and plasma of myasthenia gravis patients.

Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder where acetylcholine receptor (AChR) antibodies induce membrane attack complex formation at the muscle membrane. The C1-inhibitor (C1-INH) regulates the classical pathway and is a promising marker in other autoimmune disorders. Treatment options for AChR antibody MG include complement inhibitors; nevertheless, the early pathway activation in MG remains unclear. Serum and plasma C1s-C1-INH levels were higher in MG patients than in matched healthy controls, supporting early classical pathway activation in most MG patients. These findings allow prospective validation studies of activated C1s as a putative treatment target and potential accompanying biomarker in MG.

Transfusing maternal blood to her newborn baby-irrespective of ABO mismatch.

Background: Though blood transfusions are the common procedures in pediatric patients, transfusion reactions are rare in children. Though in adults, uncross-matched ABO group-specific blood is used in emergencies, there are no such reports in neonates and children. There are stray case reports about transfusing maternal blood for her baby and maternal blood is de facto compatible regardless of an ABO mismatchObjective: Confirming our previous hypothesis that maternal blood is compatible with her baby's blood; and maternal blood can be used for transfusion in her newborn baby irrespective of ABO match/ mismatch.Design: Prospective interventional study.Setting and Participants: Fifty-one mother-baby pairs were recruited attending Pediatric Unit of our Community Hospital from 15 July 2013 to 13 July 2015. After obtaining consent from the parents, all the required lab tests were done. Since all lab reports were favourable; these babies qualified for transfusion of maternal blood.Interventions: Fifty-one sick newborns were transfused fresh whole maternal blood as a part of treatment; irrespective of mother-baby ABO match or mismatch.Results: All babies tolerated maternal blood well and showed significant and rapid improvement. Minimum period of observation was from a minimum of 32 to a maximum of 56 months. All the babies showed good growth and development.Conclusion: By observing a particular protocol and procedural techniques, mother's blood may be used for transfusion in her own baby in neonatal period, irrespective of ABO mismatch.Significance: This is probably the largest series in world literature of 51 newborns being transfused maternal blood either ABO match or mismatch.

Visualization and Quantification of Post-stroke Neural Connectivity and Neuroinflammation Using Serial Two-Photon Tomography in the Whole Mouse Brain.

Whole-brain volumetric microscopy techniques such as serial two-photon tomography (STPT) can provide detailed information on the roles of neuroinflammation and neuroplasticity throughout the whole brain post-stroke. STPT automatically generates high-resolution images of coronal sections of the entire mouse brain that can be readily visualized in three dimensions. We developed a pipeline for whole brain image analysis that includes supervised machine learning (pixel-wise random forest models via the "ilastik" software package) followed by registration to a standardized 3-D atlas of the adult mouse brain (Common Coordinate Framework v3.0; Allen Institute for Brain Science). These procedures allow the detection of cellular fluorescent signals throughout the brain in an unbiased manner. To illustrate our imaging techniques and automated image quantification, we examined long-term post-stroke motor circuit connectivity in mice that received a motor cortex photothrombotic stroke. Two weeks post-stroke, mice received intramuscular injections of pseudorabies virus (PRV-152), a trans-synaptic retrograde herpes virus driving expression of green fluorescent protein (GFP), into the affected contralesional forelimb to label neurons in descending tracts to the forelimb musculature. Mice were sacrificed 3 weeks post-stroke. We also quantified sub-acute neuroinflammation in the post-stroke brain in a separate cohort of mice following a 60 min transient middle cerebral artery occlusion (tMCAo). Naive e450+-labeled splenic CD8+ cytotoxic T cells were intravenously injected at 7, 24, 48, and 72 h post-tMCAo. Mice were sacrificed 4 days after stroke. Detailed quantification of post-stroke neural connectivity and neuroinflammation indicates a role for remote brain regions in stroke pathology and recovery. The workflow described herein, incorporating STPT and automated quantification of fluorescently labeled features of interest, provides a framework by which one can objectively evaluate labeled neuronal or lymphocyte populations in healthy and injured brains. The results provide region-specific quantification of neural connectivity and neuroinflammation, which could be a critical tool for investigating mechanisms of not only stroke recovery, but also a wide variety of brain injuries or diseases.

The Emerging Role of Inhaled Heroin in the Opioid Epidemic: A Review.

Importance: Opioid addiction affects approximately 2.4 million Americans. Nearly 1 million individuals, including a growing subset of 21 000 minors, abuse heroin. Its annual cost within the United States amounts to $51 billion. Inhaled heroin use represents a global phenomenon and is approaching epidemic levels east of the Mississippi River as well as among urban youth. Chasing the dragon (CTD) by heating heroin and inhaling its fumes is particularly concerning, because this method of heroin usage has greater availability, greater ease of administration, and impressive intensity of subjective experience (high) compared with sniffing or snorting, although it also has a safer infectious profile compared with heroin injection. This is relevant owing to peculiar and often catastrophic brain complications. Following the American Medical Association Opioid Task Force mandate, we contribute a description of the pharmacology, pathophysiology, clinical spectrum, neuroimaging, and neuropathology of CTD leukoencephalopathy, as distinct from other heroin abuse modalities. Observations: The unique spectrum of CTD-associated health outcomes includes an aggressive toxic leukoencephalopathy with pathognomonic neuropathologic features, along with sporadic instances of movement disorders and hydrocephalus. Clinical CTD severity is predominantly moderate at admission, frequently unmodified at discharge, and largely improved in the long term. Mild cases survive with minor sequelae, while moderate to severe presentations might deteriorate and progress to death. Other methods of heroin use may complicate with stroke, seizure, obstructive hydrocephalus, and (uncharacteristically) leukoencephalopathy. Conclusions and Relevance: The distinct pharmacology of CTD correlates with its specific clinical and radiological features and prompts grave concern for potential morbidity and long-term disability costs. Proposed diagnostic criteria and standardized reporting would ameliorate the limitations of CTD literature and facilitate patient selection for a coenzyme Q10 therapeutic trial.

Effects of two high dose vitamin-D by parenteral route in treating vitamin-D deficiency: a prospective interventional study.

Vitamin D deficiency is recognized as a global public health problem. Despite ample sunshine, vitamin D deficiency is very common in the Middle East (15°-36°N) and African (35°S-37°N) countries; and in South Asian countries. Different oral or parenteral dose modalities are tried for treatment of vitamin-D deficiency. Since the duration of corrective therapy is long; compliance of patients is a major issue. Herein we suggest a simple, affordable and practical plan to treat this very common deficiency.

Effect of two high dose vitamin D by parenteral route in treating vitamin D deficiency a prospective interventional study.

BACKGROUND: Vitamin D deficiency is recognized as a global public health problem. Despite ample sunshine, vitamin D deficiency is very common in the Middle East (15°-36°N) and African (35°S-37°N) countries; and in South Asian countries. AIM: To find a simple, affordable and practical plan to treat vitamin-d deficiency. TYPE OF STUDY: This was a prospective interventional study. OUTCOME VARIABLE: The primary outcome was typed as vitamin-D level more than 50 nanograms/ml as 'yes' and poor response or 'no' when it was less than 50 ng/ml. PARTICIPANTS: 80 Women participated in study. Laboratory tests: Vitamin D [25-OHD]-estimations were performed with LCMSMS-liquid chromatography tandem mass spectrometry. Corrective vitamin-D doses: All participants received TWO doses of Vitamin-D injections one ml at a time [600K IU/ml or 600,000 IU/ml]. All participants received their first dose; after collecting blood samples for Vitamin-D estimations. Second dose was given about a month after the first one [range 30-37 days]. These doses were given to correct the deficiency. RESULTS: Even with this high dose treatment 60% woman had unsatisfactory Vitamin-D levels.

Shuffling Adaptive Clinical Trials.

Clinical trials are interventional studies on human beings, designed to test the hypothesis for diagnostic techniques, treatments, and disease preventions. Any novel medical technology should be evaluated for its efficacy and safety by clinical trials. The costs associated with developing drugs have increased dramatically over the past decade, and fewer drugs are obtaining regulatory approval. Because of this, the pharmaceutical industry is continually exploring new ways of improving drug developments, and one area of focus is adaptive clinical trial designs. Adaptive designs, which allow for some types of prospectively planned mid-study changes, can improve the efficiency of a trial and maximize the chance of success without undermining validity and integrity of the trial. However it is felt that in adaptive trials; perhaps by using accrued data the actual patient population after the adaptations could deviate from the originally target patient population and so to overcome this drawback; special methods like Bayesian Statistics, predicted probability are used to deduce data-analysis. Here, in this study, mathematical model of a new adaptive design (shuffling adaptive trial) is suggested which uses real-time data, and because there is no gap between expected and observed data, statistical modifications are not needed. Results are obviously clinically relevant.

Transfusion-associated graft versus host disease (TAGVHD)--with reference to neonatal period.

Transfusion-associated graft versus host disease [TAGVHD] results from the engraftment of transfused immuno-competent cells in blood transfusion recipients, whose immune system is unable to reject them. All blood products containing viable, immuno-competent T cells have been implicated in TAGVHD. Presence of a "one-way HLA match between donor and recipient" is associated with a significantly increased risk of TAGVHD. Though sharing of haplotype is the most probable explanation, it is far from adequate. Since TAGVHD is not seen in patients with AIDS, and an acute GVHD-like syndrome has been noted in some identical twins and autologous (self) transplants, some other processes, possibly of an "autoimmune" nature are responsible for TAGVHD. Most of the cases have been reported from Japan. This clustering in space and time is rather intriguing. We offer here alternative hypothesis. Foetal and then neonatal lymphocytes exhibit tolerance towards donor cytotoxic T lymphocytes; and consequently very few cases of TAGVHD have been reported in neonates than expected. This tolerance is a part of altered immunology of pregnancy. We feel that it is possible to use maternal blood for transfusion to her newborn baby by following certain protocol and procedure and TAGVHD is no barrier.

Thrombolysis in ischemic stroke without arterial occlusion at presentation.

BACKGROUND AND PURPOSE: None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. METHODS: We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). RESULTS: A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01). CONCLUSIONS: This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis.

Use of pipeline flow diverting stents for wide neck intracranial aneurysms: A retrospective institutional review.

BACKGROUND: Intracranial aneurysms (ICA) if inadequately treated may result in serious morbidity and mortality. Wide-neck; large/giant, fusiform, and dissecting aneurysms are not well treated using the conventional coil embolization technique. Recent advance in endovascular treatment and technology has introduced flow diverter devices including pipeline embolization devices (PED) and Silk stents that have been shown to be more effective in treating these more complicated aneurysms. Flow Diverter devices offer a more physiologic approach to ICA treatment. METHODS: We conducted a retrospective chart review of 23 adult patients who underwent aneurysm treatment utilizing the pipeline stent at Duke University Medical Center from July 2011 to March 2013. RESULTS: Majority of patients (19, 82.7%) showed angiographic evidence of complete obliteration of aneurysm at 6 months follow-up, with sustained clinical improvement on modified Rankin scale score. All of the patients tolerated the procedure well with no intra-operative hemorrhage or intra-operative thromboembolic complications. CONCLUSIONS: Our experience shows that use of PED offers a safe and effective strategy for treatment of complex ICA. Larger prospective studies are needed to confirm these observations.

Comparison of surgical and endovascular approach in management of spinal dural arteriovenous fistulas: A single center experience of 27 patients.

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) is a rare spinal vascular malformation with an annual incidence of 5-10 cases per million. The data on efficacy, recurrence rates and complications of endovascular versus surgical treatment of SDAVF is limited. METHODS: We conducted a retrospective chart review of 27 adult patients with a diagnosis of SDAVF and who underwent treatment at Duke University Hospital between January 1, 1993 and December 31, 2012. We compared the outcome measures by Aminoff-Logue score (ALS) in patients who underwent treatment with endovascular embolization versus surgical ligation of fistula. We compared complication rates, recurrence rates as well as data on long-term follow up in these patients. RESULTS: Out of 27 patients in the study, 10 patients underwent endovascular embolization (Onyx was used in 5 patients and NBCA in 5 patients) as the first line therapy. Seventeen patients underwent surgical ligation as initial therapeutic modality. Patients in both groups showed significant improvement in clinical status (ALS) after treatment. One patient in endovascular group developed spinal infarction due to accidental embolization of medullary artery. Three patients in embolization group had recurrence of fistula during the course of follow up requiring surgical ligation. Two patients in surgical group developed local wound infection. None of the patients in surgical group had recurrence of fistula during the course of follow up. CONCLUSIONS: Endovascular embolization and surgical ligation are effective treatment strategies for SDAVF. Our observations show that surgical ligation may offer permanent cure without any recurrence. Endovascular approach is associated with higher incidence of recurrence, especially with use of onyx.

Recovery of swallowing after dysphagic stroke: an analysis of prognostic factors.

BACKGROUND: Dysphagia is a major complication of stroke, but factors influencing its recovery are incompletely understood. The goal of this study was to identify important prognostic variables affecting swallowing recovery after acute ischemic stroke. METHODS: We retrospectively reviewed our patient database to identify acute ischemic stroke patients who developed dysphagia after stroke but were free of other confounding conditions affecting swallowing. Of the 1774 patients screened, 323 met the study criteria. We assessed the effect of age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, level of consciousness (LOC), facial weakness, dysarthria, neglect, bihemispheric infarcts, right hemispheric infarcts, brainstem infarcts, intubation, aspiration, acute stroke therapies, occurrence of symptomatic hemorrhagic transformation, seizures, pneumonia, and length of hospitalization (LOH) on persistence of dysphagia at hospital discharge in a logistic regression analysis. RESULTS: The mean age and NIHSS scores (mean ± standard deviation) were 75.9 ± 13.6 years and 13.5 ± 6.9, respectively; 58.5% were women. In a multivariate analysis, aspiration detected on a clinical swallowing evaluation (odds ratio [OR] 21.83; 95% confidence interval [CI] 8.16-58.42; P < .0001), aspiration on videofluoroscopic swallowing study (OR 10.50; 95% CI 3.35-32.96; P < .0001), bihemispheric infarcts (OR 3.72; 95% CI 1.33-10.43; P = .0123), dysarthria (OR 3.4; 95% CI 1.57-7.35; P = .0019), intubation (OR 2.86; 95% CI 1.10-7.39; P = .0301), NIHSS score ≥12 (OR 2.51; 95% CI 1.19-5.23; P = .0157) were significant predictors of persistent dysphagia. The area under the curve and Somer's Dxy statistics of the model were 0.8918 and 0.78, respectively, indicating good calibration and discriminative power. CONCLUSIONS: Prognostic factors affecting swallowing recovery identified in this study can help advance dysphagia research methodologies and the clinical care of stroke patients.

Therapeutic advances in understanding pathophysiology and treatment of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis is an important cause of stroke in young population. A thorough understanding of its pathophysiology, clinical, and radiological features is needed for an early and timely diagnosis to initiate appropriate treatment before the disease becomes worse and difficult to manage. In this study, the recent advances in the therapeutics of cerebral venous thrombosis with brief overview of epidemiology, clinical features, and imaging modalities were reviewed. With emerging imaging modalities and therapeutic options, there has been a progress in ease of ability to diagnose and treat cerebral venous thrombosis, but because of the lack of a much-needed randomized controlled trial, there is deficiency of a standardized algorithm/protocol for treatment of cerebral sinus thrombosis, which remains mostly at the discretion of experiences of treating physicians. In this study, the presently available treatment and diagnostic modalities with pros and cons of each of them were reviewed.