Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth

Capillary malformations are slow-flow vascular malformations that affect the microcirculation including capillaries and post capillary venules and can be associated with growth differences. Specifically, the association of capillary malformations with undergrowth is a vastly understudied vascular syndrome with few reports of genetic causes including PIK3CA, GNAQ, and GNA11. Recently, a somatic pathogenic variant in AKT3 was identified in one child with a cutaneous vascular syndrome similar to cutis marmorata telangiectatica congenita, undergrowth, and no neurodevelopmental features. Here, we present a male patient with a capillary malformation and undergrowth due to a somatic pathogenic variant in AKT3 to confirm this association. It is essential to consider that mosaic pathogenic variants in AKT3 can cause a wide spectrum of disease. There is a need for future studies focusing on capillary malformations with undergrowth to understand the underlying mechanism.     

Development and pretesting of “Becoming Breastfeeding Friendly”: Empowering governments for global scaling up of breastfeeding programmes

Scaling up breastfeeding programmes has not been highly prioritized despite overwhelming evidence that breastfeeding benefits the health of mothers and children. Lack of evidence‐based tools for scaling up may deter countries from prioritizing breastfeeding. To fill this gap, Becoming Breastfeeding Friendly (BBF) was developed to guide countries in effectively scaling up programmes to protect, promote, and support breastfeeding. BBF includes an evidence‐based toolbox that consists of a BBF Index, case studies, and a 5‐meeting process. These three interrelated components enable countries to assess their breastfeeding scaling up environment, identify gaps, propose policy recommendations, develop a scaling up plan, and track progress. The toolbox was developed based on current evidence and expert guidance from a Technical Advisory Group, which was composed of global breastfeeding and metric experts with experience in the scaling up of health and nutrition programmes in low‐, middle‐, and high‐income countries. The BBF toolbox required a step‐by‐step iterative approach to describe and systematize each component, thus an operational manual was developed. The BBF toolbox and BBF operational manual underwent intensive pretesting in two countries, Ghana and Mexico, resulting in the modification of each component plus the operational manual. Pretesting continues in six additional countries demonstrating that BBF is a robust and dynamic multi‐sectoral process that, with relatively minor adaptations, can be successfully implemented in countries across world regions.     

Thrombotic thrombocytopenic purpura in a postoperative patient taking cephalexin responding to plasmapheresis: A case report and review of cephalosporin‐induced TTP

The clinical presentation of thrombotic thrombocytopenic purpura (TTP) is often atypical delaying diagnosis and treatment. A number of drugs have been implicated in the development of TTP, including cyclosporine, tacrolimus, clopidogrel, and quinine. To our knowledge, only three cases of cephalosporin‐induced TTP have been described, with two of these cases occurring with these use of cephalexin. We herein describe a case of TTP occurring in a postoperative patient taking cephalexin, requiring plasmapheresis. Following plasmapheresis, the patient's mental status and platelet count significantly improved. J. Clin. Apheresis 31:473–475, 2016. © 2015 Wiley Periodicals, Inc.     

Quantifying the therapeutic requirements and potential for combination therapy to prevent bacterial coinfection during influenza

Secondary bacterial infections (SBIs) exacerbate influenza-associated disease and mortality. Antimicrobial agents can reduce the severity of SBIs, but many have limited efficacy or cause adverse effects. Thus, new treatment strategies are needed. Kinetic models describing the infection process can help determine optimal therapeutic targets, the time scale on which a drug will be most effective, and how infection dynamics will change under therapy. To understand how different therapies perturb the dynamics of influenza infection and bacterial coinfection and to quantify the benefit of increasing a drug’s efficacy or targeting a different infection process, I analyzed data from mice treated with an antiviral, an antibiotic, or an immune modulatory agent with kinetic models. The results suggest that antivirals targeting the viral life cycle are most efficacious in the first 2 days of infection, potentially because of an improved immune response, and that increasing the clearance of infected cells is important for treatment later in the infection. For a coinfection, immunotherapy could control low bacterial loads with as little as 20 % efficacy, but more effective drugs would be necessary for high bacterial loads. Antibiotics targeting bacterial replication and administered 10 h after infection would require 100 % efficacy, which could be reduced to 40 % with prophylaxis. Combining immunotherapy with antibiotics could substantially increase treatment success. Taken together, the results suggest when and why some therapies fail, determine the efficacy needed for successful treatment, identify potential immune effects, and show how the regulation of underlying mechanisms can be used to design new therapeutic strategies.