Case Report: An unusual case of priapism

No Abstrac

Anti-tumor activity without on-target off-tumor toxicity of GD2-Chimeric Antigen Receptor T cells in patients with neuroblastoma

The reprogramming of a patient’s immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥108/meter2 CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity

The vaccination of 35,000 dogs in 20 working days using combined static point and door-to-door methods in Blantyre, Malawi

An estimated 60,000 people die of rabies annually. The vast majority of cases of human rabies develop following a bite from an infected dog. Rabies can be controlled in both human and canine populations through widespread vaccination of dogs. Rabies is particularly problematic in Malawi, costing the country an estimated 13 million USD and 484 human deaths annually, with an increasing paediatric incidence in Blantyre City. Consequently, the aim of this study was to vaccinate a minimum of 75% of all the dogs within Blantyre city during a one month period. Blantyre's 25 administrative wards were divided into 204 working zones. For initial planning, a mean human:dog ratio from the literature enabled estimation of dog population size and dog surveys were then performed in 29 working zones in order to assess dog distribution by land type. Vaccination was conducted at static point stations at weekends, at a total of 44 sites, with each operating for an average of 1.3 days. On Monday to Wednesday, door-to-door vaccination sessions were undertaken in the areas surrounding the preceding static point stations. 23,442 dogs were vaccinated at static point stations and 11,774 dogs were vaccinated during door-to-door vaccinations. At the end of the 20 day vaccination programme, an assessment of vaccination coverage through door-to-door surveys found that of 10,919 dogs observed, 8,661 were vaccinated resulting in a vaccination coverage of 79.3% (95%CI 78.6-80.1%). The estimated human:dog ratio for Blantyre city was 18.1:1. Mobile technology facilitated the collection of data as well as efficient direction and coordination of vaccination teams in near real time. This study demonstrates the feasibility of vaccinating large numbers of dogs at a high vaccination coverage, over a short time period in a large African city

Cronobacter spp. as emerging causes of healthcare-associated infection

Background: Until recently, members of the Cronobacter genus (formerly known as Enterobacter sakazakii) were a relatively unknown cause of nosocomial infections. However, their association with infant infections, particularly through the consumption of contaminated reconstituted infant formula in neonatal intensive care units, has resulted in international efforts to improve neonatal health care. Aim: To investigate current understanding of this emergent group of bacterial pathogens and the steps taken to reduce neonatal infection. Methods: A literature review was undertaken to determine current knowledge of the Cronobacter genus with respect to recent taxonomic revisions, sources and clinical relevance. Findings: The majority of severe neonatal meningitis infections are associated with one of the 10 Cronobacter spp., the clonal complex known as C. sakazakii sequence type 4. International efforts by the Food and Agriculture Organization–World Health Organization (WHO) to reduce the risk of neonatal infection by this organism have resulted in improved microbiological safety of powdered infant formula (PIF), but revised guidelines for feeding practices have been problematic. In addition, the majority of infections occur in the adult population and the sources are unknown. Conclusion: International improvements in the microbiological safety of PIF and advice on feeding practices have focused on improving neonatal health care following the heightened awareness of Cronobacter infections in this particular age group. These measures are also likely to reduce neonatal exposure to other opportunistic bacterial pathogens, but a number of unresolved issues remain with respect to the practicalities of feeding premature neonates safely while following WHO advice

Barriers of attendance to dog rabies static point vaccination clinics in Blantyre, Malawi

<div><p>Rabies is a devastating yet preventable disease that causes around 59,000 human deaths annually. Almost all human rabies cases are caused by bites from rabies-infected dogs. A large proportion of these cases occur in Sub Saharan Africa (SSA). Annual vaccination of at least 70% of the dog population is recommended by the World Health Organisation in order to eliminate rabies. However, achieving such high vaccination coverage has proven challenging, especially in low resource settings. Despite being logistically and economically more feasible than door-to-door approaches, static point (SP) vaccination campaigns often suffer from low attendance and therefore result in low vaccination coverage. Here, we investigated the barriers to attendance at SP offering free rabies vaccinations for dogs in Blantyre, Malawi. We analysed data for 22,924 dogs from a city-wide vaccination campaign in combination with GIS and household questionnaire data using multivariable logistic regression and distance estimation techniques. We found that distance plays a crucial role in SP attendance (i.e. for every km closer the odds of attending a SP point are 3.3 times higher) and that very few people are willing to travel more than 1.5 km to bring their dog for vaccination. Additionally, we found that dogs from areas with higher proportions of people living in poverty are more likely to be presented for vaccination (ORs 1.58-2.22). Furthermore, puppies (OR 0.26), pregnant or lactating female dogs (OR 0.60) are less likely to be presented for vaccination. Owners also reported that they did not attend an SP because they were not aware of the campaign (27%) or they could not handle their dog (19%). Our findings will inform the design of future rabies vaccination programmes in SSA which may lead to improved vaccination coverage achieved by SP alone.</p></div