Persistent Multiyear Control of Relapsed T‐Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report

There are few therapeutic options for patients with T‐cell acute lymphoblastic leukemia (T‐ALL) who have recurrent disease after initial matched sibling hematopoietic stem cell transplantation. While a second hematopoietic stem cell transplant (HSCT) from a haploidentical donor offers the conceptual possibility of greater graft versus leukemia effect, there is minimal literature to describe the efficacy of this approach in recurrent pediatric T‐ALL. We present the case of a now 9‐year‐old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life.     

Successful Retreatment of a Child with a Refractory Brainstem Ganglioglioma with Vemurafenib

A child with brainstem ganglioglioma underwent subtotal resection and focal radiation. Magnetic resonance imaging confirmed tumor progression 6 months later. Another partial resection revealed viable BRAF V600E‐positive residual tumor. Vemurafenib (660 mg/m²/dose) was administered twice daily, resulting in >70% tumor reduction with sustained clinical improvement for 1 year. Vemurafenib was then terminated, but significant tumor progression occurred 3 months later. Vemurafenib was restarted, resulting in partial response. Toxicities included Grade I pruritus and Grade II rash. Vemurafenib was effectively crushed and administered in solution via nasogastric tube. We demonstrate benefit from restarting vemurafenib therapy.     

Identification of bacteria associated with spreading odontogenic infections by 16S rRNA gene sequencing.

OBJECTIVE: To determine the bacterial species associated with spreading odontogenic infections (SOIs). STUDY DESIGN: Pus samples from 4 cases of SOI were analyzed by microbiological culture methods for the presence of bacteria, and by polymerase chain reaction (PCR) amplification, cloning, and sequencing of bacterial 16S rRNA genes. RESULTS: Culture methods identified species from the genera Prevotella, Streptococcus, and Fusobacterium, as well as anaerobic streptococci. Molecular detection methods identified a far more diverse microflora. The predominant genus detected was Prevotella, representing 102 (50.2%) of 203 clones analyzed. Prevotella oris was the most abundant species identified, representing 45 (22.2%) of 203 clones analyzed. Twelve clones (5.9%) represented uncultivable species, namely Prevotella PUS9.180, an uncultured Peptostreptococcus species, and an uncultured bacterium belonging to the Bacteroidetes phylum. CONCLUSIONS: Prevotella species may play an important role in SOIs, and further work to examine in more detail the pathogenicity determinants of these organisms and associated host responses is warranted.     

Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of CaV2.1 Ca2+ channel--loss-of-function cellular model of SCA6

Spinocerebellar ataxia (SCA) 6 is caused by small expansion of a polyglutamine sequence, encoded by CAG trinucleotide repeats, at the C-terminal end of the human CaV2.1 (P/Q-type) Ca2+ channel alpha12.1 subunit and it manifests itself as slowly progressive cerebellar ataxia. To elucidate the pathogenic mechanisms underlying SCA6, we introduced CAG repeats of various lengths into the Ca2+ channel alpha12.1 subunit cDNA and expressed them in baby hamster kidney cells stably expressing the auxiliary subunits (alpha2delta and beta4). The occurrence of cell death differed between cells transfected with the normal and mutant Ca2+ channels under the condition of serum starvation plus potassium-induced depolarization, and Cdk inhibition elucidated the differences more clearly. The CaV2.1 (P/Q-type) Ca2+ channel-specific blocker omega-agatoxin IVA abolished the cell-death-preventing effect of the normal Ca2+ channel. Together with our previous finding that the polyglutamine expansion in SCA6 interferes with the Ca2+ channel to reduce Ca2+ influx, these results indicate that impaired function of the mutant Ca2+ channels rendered them unable to prevent cell death.     

Creation and Implementation of an Outpatient Pathway for Atrial Fibrillation in the Emergency Department Setting: Results of an Expert Panel

Atrial fibrillation and flutter (AF) is a common condition among emergency department (ED) patients in the United States. Traditionally, ED care for primary complaints related to AF focus on rate control, and patients are often admitted to an inpatient setting for further care. Inpatient care may include further telemetry monitoring and diagnostic testing, rhythm control, a search for identification of AF etiology, and stroke prophylaxis. However, many patients are eligible for safe and effective outpatient management pathways. They are widely used in Canada and other countries but less widely adopted in the United States. In this project, we convened an expert panel to create a practical framework for the process of creating, implementing, and maintaining an outpatient AF pathway for emergency physicians to assess and treat AF patients, safely reduce hospitalization rates, ensure appropriate stroke prophylaxis, and effectively transition patients to longitudinal outpatient treatment settings from the ED and/or observation unit. To support local pathway creation, the panel also reached agreement on a protocol development plan, a sample pathway, consensus recommendations for pathway components, sample pathway metrics, and a structured literature review framework using a modified Delphi technique by a technical expert panel of emergency medicine, cardiology, and other stakeholder groups.     

Paying participants in addiction research: Is cash king?

I know there’s some real scary, hardcore stories of people selling vouchers, but I’ve never experienced anything like that. If I got a voucher, I would often see it as a bonus. If it was for a shop I didn’t use, I would sell it to someone I knew for the same amount of money – them just doing me a favour really. I wouldn’t sell a voucher for less than its value.