The effect of rituximab on anti-platelet autoantibody levels in patients with immune thrombocytopenia.

Rituximab is an effective therapy resulting in a platelet count improvement in 60% of patients with immune thrombocytopenia (ITP). Rituximab depletes B cells; thus, a reduction in platelet autoantibody levels would be anticipated in patients who achieve a clinical response to this treatment. The objectives of this study were to determine whether rituximab was associated with a reduction in platelet autoantibody levels, and to correlate the loss of autoantibodies with the achievement of a treatment response. We performed a case-control study nested within a previous randomized controlled trial of standard therapy plus adjuvant rituximab or placebo. We measured platelet-bound anti-glycoprotein (GP) IIbIIIa and anti-GPIbIX using the antigen capture test. Of 55 evaluable patients, 25 (45%) had a detectable platelet autoantibody at baseline. Rituximab was associated with a significant reduction in anti-GPIIbIIIa levels (P = 0·02) but not anti-GPIbIX levels (P = 0·51) compared with placebo. Neither the presence of an autoantibody at baseline nor the loss of the autoantibody after treatment was associated with a response to rituximab. The subset of patients with persistent autoantibodies after treatment failed to achieve a platelet count response, suggesting that persistence of platelet autoantibodies can be a marker of disease severity.

Morphological Variations of Explosive Residue Particles and Implications for Understanding Detonation Mechanisms.

The possibility of recovering undetonated explosive residues following detonation events is well-known; however, the morphology and chemical identity of these condensed phase postblast particles remains undetermined. An understanding of the postblast explosive particle morphology would provide vital information during forensic examinations, allowing rapid initial indication of the explosive material to be microscopically determined prior to any chemical analyses and thereby saving time and resources at the crucial stage of an investigation. In this study, condensed phase particles collected from around the detonations of aluminized ammonium nitrate and RDX-based explosive charges were collected in a novel manner utilizing SEM stubs. By incorporating the use of a focused ion beam during analysis, for the first time it is possible to determine that such particles have characteristic shapes, sizes, and internal structures depending on the explosive and the distance from the detonation at which the particles are recovered. Spheroidal particles (10-210 µm) with microsurface features recovered following inorganic charge detonations were dissimilar to the irregularly shaped particles (5-100 µm) recovered following organic charge firings. Confirmatory analysis to conclude that the particles were indeed explosive included HPLC-MS, Raman spectroscopy, and mega-electron volt-secondary ionization mass spectrometry. These results may impact not only forensic investigations but also the theoretical constructs that govern detonation theory by indicating the potential mechanisms by which these particles survive and how they vary between the different explosive types.

Producing megakaryocytes from a human peripheral blood source.

BACKGROUND: Cultured megakaryocytes could prove useful in the study of human diseases, but it is difficult to produce sufficient numbers for study. We describe and evaluate the use of an expansion process to develop mature megakaryocytes from peripheral blood-derived human hematopoietic stem and progenitor cells (HSPCs). STUDY DESIGN AND METHODS: HSPCs (CD34+) were isolated from peripheral blood by positive selection and expanded using an optimal CD34+ expansion supplement. We evaluated megakaryocyte growth, maturation, and morphology in response to thrombopoietin (TPO) stimulation using flow cytometry and electron microscopy. TPO demonstrated a dose-dependent stimulatory effect on both megakaryocyte number and maturation. RESULTS: From 90 to 120 mL of unmanipulated peripheral blood, we isolated a mean of 1.5 × 10(5) HSPCs (1.5 × 10(3) cells/mL of whole blood). HSPCs expanded nine-fold after a 4-day culture using an expansion supplement. Expanded cells were cultured for an additional 8 days with TPO (20 ng/mL), which resulted in a 2.9-fold increase in megakaryocytic cells where 83% of live cells expressed CD41a+, a marker of megakaryocyte commitment, and 50% expressed CD42b+, a marker for megakaryocyte maturation. The expanded HSPCs responded to TPO stimulation to yield more than 1.0 × 10(6) megakaryocytes. This cell number was sufficient for morphologic studies that demonstrated these expanded HSPCs produced mature polyploid megakaryocytes capable of forming proplatelet extensions. CONCLUSIONS: Peripheral blood HSPCs can be expanded and differentiated into functional, mature megakaryocytes, a finding that supports the use of this process to study inherent platelet (PLT) production disorders as well as study factors that impair normal PLT production.

The spatial distribution of postblast RDX residue: forensic implications.

Locating exactly where trace explosive residue samples should be sought during sample collection at bomb scenes is not specified in the published literature or guidelines; in this area, it is generally acknowledged that forensic practices are based on tradition rather than evidence. This study investigated patterns in the spatial distribution of postblast 1,3,5-trinitro-1,3,5-triazocyclohexane residue from a series of unconfined detonations, over a range of sampling sites, and at two different detonation heights. The amount of residue recovered from the sites decreased as a function of distance from the center of the explosion. [Correction added after online publication 27 December 2012: In the preceding sentence, "increased" was corrected to "decreased" to agree with the conclusion of the article.] As the height of the detonations increased, more residues were found from all sampling sites. The findings of this empirical study have a number of important practical implications including determining where residue samples are best sought at crime scenes.

Cerebral venous sinus thrombosis as the initial presentation of essential thrombocythemia - A case report and literature review.

Myeloproliferative disorders (MPD) are associated with vascular thrombosis. Common sites for thrombosis are large arteries; however, less commonly, cerebral venous sinus thrombosis (CVST) has also been reported. It is rare to have CVST as an initial presentation of MPD. We discuss a male patient in whose presentation due to CVST led to the diagnosis of essential thrombocythemia (ET). Furthermore, we performed a literature review to evaluate the association of CVST with ET.

COVID-19 Associated Imported Plasmodium vivax Malaria Relapse: First Reported Case and Literature Review.

Plasmodium vivax (P. vivax) is a protozoan parasite that causes vivax malaria. Disease relapse post-treatment is reported in P. vivax co-infection with other bacterial and parasitic infections, but Plasmodium vivax reactivation is not very common with viral infections. Early recognition and diagnosis of a Plasmodium vivax malaria relapse in a non-endemic region pose a diagnostic dilemma. COVID-19 co-infection compounds this dilemma due to overlapping symptoms. Early diagnosis and treatment are essential for a favorable clinical outcome. We report a middle-aged gentleman with high-grade fever and headaches who had COVID-19 and was found to have a relapse of Plasmodium vivax malaria.

Postdischarge 24/7 Hotline Service for Neurology and Neurosurgery Patients and 1-Year Impact on Readmission Rates, Unplanned Emergency Department Visits, and Patient Satisfaction.

OBJECTIVE: Telephone triage is a system in which trained nurses use standardized protocols to evaluate symptoms over the phone and determine the appropriate course of action. MATERIALS AND METHODS: We implemented a protocol for systematic follow up phone calls and telephonic triage to families of neurology and neurosurgery patients after discharge, primarily to improve care transition and to assess its impact on the ratio of visits in the emergency department, readmissions, and overall satisfaction of patients and families. The intervention comprised the implementation of nurse led telephone triage and postdischarge follow up phone calls. After implementing hotline services in mind and brain service line, a retrospective cohort study was conducted to evaluate the impact of hotline services on patient readmissions, emergency department visits, and overall satisfaction rate. We collected data of readmission rate and emergency visits of discharge patients in three periods a prehotline period, immediate posthotline period, and late posthotline period to make comparison. Patients discharged home from the neurology and neurosurgery services from January 2017 to September 2019 were provided with hotline number to call in case of any issue or query. These patients also received postdischarge follow up calls from hotline nurses. We initiated the hotline in October 2017. RESULTS: On analysis, we found a 25% decline in readmission rate in the immediate period of hotline followed by a further decline to 37.2% in the late period as compared to the prehotline period. Among discharge patients visiting the emergency department, we found a decline of 18.5% in the immediate posthotline period which further declined to 77.7% in the later phase as compared to the prehotline period. CONCLUSION: A standardized telephone system and pathway can be an effective way to improve nurse-patient communication which can further improve health outcomes for many patients.

Need of Physical and Chemical Restraints: Experiences at Inpatient Psychiatric Ward in a Tertiary Care Hospital in Karachi, Pakistan.

In psychiatry, agitated / aggressive patients are often treated with de-escalation techniques. If this does not work, physical or chemical restrains are required; but in the event of resistance, seclusion is applied. We report the findings of baseline study of experiences of physical and chemical restraints in a tertiary care hospital in Karachi, where 104 files were evaluated retrospectively. The mean age of patients was 32.5 ±14.3 years with 54.8% men, while the average length of stay was 11.5 ±9.3 days. Agitation, violent behaviour, and aggression were the most common indications for restraints. In total, 94.5% of patients had both physical and chemical restraints with the latter being used as the first choice in 70 patients; whereas, 67.1% of patients' families were not informed before application of restraints. The seclusion need assessment was conducted in 4.1% of patients.

The spatial distribution patterns of condensed phase post-blast explosive residues formed during detonation.

The continued usage of explosive devices, as well as the ever growing threat of 'dirty' bombs necessitates a comprehensive understanding of particle dispersal during detonation events in order to develop effectual methods for targeting explosive and/or additive remediation efforts. Herein, the distribution of explosive analytes from controlled detonations of aluminised ammonium nitrate and an RDX-based explosive composition were established by systematically sampling sites positioned around each firing. This is the first experimental study to produce evidence that the post-blast residue mass can distribute according to an approximate inverse-square law model, while also demonstrating for the first time that distribution trends can vary depending on individual analytes. Furthermore, by incorporating blast-wave overpressure measurements, high-speed imaging for fireball volume recordings, and monitoring of environmental conditions, it was determined that the principle factor affecting all analyte dispersals was the wind direction, with other factors affecting specific analytes to varying degrees. The dispersal mechanism for explosive residue is primarily the smoke cloud, a finding which in itself has wider impacts on the environment and fundamental detonation theory.

Photo-induced enhanced Raman spectroscopy for universal ultra-trace detection of explosives, pollutants and biomolecules.

Surface-enhanced Raman spectroscopy is one of the most sensitive spectroscopic techniques available, with single-molecule detection possible on a range of noble-metal substrates. It is widely used to detect molecules that have a strong Raman response at very low concentrations. Here we present photo-induced-enhanced Raman spectroscopy, where the combination of plasmonic nanoparticles with a photo-activated substrate gives rise to large signal enhancement (an order of magnitude) for a wide range of small molecules, even those with a typically low Raman cross-section. We show that the induced chemical enhancement is due to increased electron density at the noble-metal nanoparticles, and demonstrate the universality of this system with explosives, biomolecules and organic dyes, at trace levels. Our substrates are also easy to fabricate, self-cleaning and reusable.