Current aesthetic use of abobotulinumtoxinA in clinical practice: an evidence-based consensus review.

The amount and complexity of scientific and clinical evidence for aesthetic use of botulinum neurotoxin type A (BoNT-A) has expanded rapidly in recent years, especially for abobotulinumtoxinA, necessitating reassessment of current knowledge about aesthetic use of abobotulinumtoxinA and other BoNT-A preparations. A committee of 13 plastic surgeons, facial plastic surgeons, and dermatologists engaged in a live discussion of information from a systematic literature review and an Internet-based survey of their beliefs and practices. The committee achieved consensus on most issues. It was concluded that doses of different BoNT-A preparations cannot be interconverted with a fixed ratio. The size of the "field of effect" is difficult to measure, and comparisons between preparations have yielded equivocal results. Nonresponse due to neutralizing antibodies appears exceedingly rare with currently available BoNT-A preparations and of little concern clinically. BoNT-A dose, injection depth, and injection technique should be adjusted according to the anatomic area being treated and each patient's individual characteristics and goals. Aesthetic use of BoNT-A has a good safety profile. Most adverse events are minor and related to the trauma of injection, although special care is needed in certain anatomic areas. Detailed recommendations for treatment of different anatomic areas are presented. BoNT-A products are often used in conjunction with other treatment modalities (eg, fillers and resurfacing), but little agreement was reached on best practices. The findings reported in this consensus document may serve as a practical guide for aesthetic practitioners as they apply the latest knowledge about BoNT-A in providing their patients with optimal care.

Safety and efficacy of activated transfected killer cells for neutropenic fungal infections.

BACKGROUND: Invasive fungal infections cause considerable morbidity and mortality in neutropenic patients. White blood cell transfusions are a promising treatment for such infections, but technical barriers have prevented their widespread use. METHODS: To recapitulate white blood cell transfusions, we are developing a cell-based immunotherapy using a phagocytic cell line, HL-60. We sought to stably transfect HL-60 cells with a suicide trap (herpes simplex virus thymidine kinase), to enable purging of the cells when desired, and a bioluminescence marker, to track the cells in vivo in mice. RESULTS: Transfection was stable despite 20 months of continuous culture or storage in liquid nitrogen. Activation of these transfected cells with retinoic acid and dimethyl sulfamethoxazole enhanced their microbicidal effects. Activated transfected killer (ATAK) cells were completely eliminated after exposure to ganciclovir, confirming function of the suicide trap. ATAK cells improved the survival of neutropenic mice with lethal disseminated candidiasis and inhalational aspergillosis. Bioluminescence and histopathologic analysis confirmed that the cells were purged from surviving mice after ganciclovir treatment. Comprehensive necropsy, histopathology, and metabolomic analysis revealed no toxicity of the cells. CONCLUSIONS: These results lay the groundwork for continued translational development of this promising, novel technology for the treatment of refractory infections in neutropenic hosts.

Optimization of a myeloid cell transfusion strategy for infected neutropenic hosts.

Although granulocyte transfusion is a logical, therapeutic option for neutropenic patients with refractory infections, significant technical barriers have prevented its widespread use. A novel phagocyte transfusion strategy has been developed based on activation of a human myeloid cell line HL-60. To further define the potential for HL-60 cells to recapitulate white cell transfusions, a shortened duration of activation was evaluated, facile quality control markers were defined, and the impact of low-dose irradiation on cell function was determined. Three days of activation resulted in increased cell viability and in vitro candidacidal capacity but with slightly higher cell replication compared with 7 days of activation. Cell viability and several flow cytometric measurements were accurate, quality control markers for HL-60 activation. In combination with activation, low-dose irradiation abrogated replication while sparing the candidacidal effects of the HL-60 cells. Infusion of irradiated, activated HL-60 cells improved survival of neutropenic, candidemic mice significantly. In summary, activated, irradiated HL-60 cells are microbicidal, have virtually no replicative capacity, and are safe and effective at protecting neutropenic mice against an otherwise 100% fatal candidal infection. With continued development, this strategy to recapitulate neutrophil functions has the potential to serve as an effective alternative to granulocyte transfusions.

Hand augmentation with Radiesse (Calcium hydroxylapatite).

The hand has remained a considerable treatment challenge, as new soft tissue fillers have arrived in the esthetic marketplace. The challenge has been the result of both the multiple visits required for treatment in, for example, autologous fat grafting and the simple management of pain in the innervated areas of the hand between the bones. This paper introduces a novel, noticeably less painful approach to treatment of the hand with calcium hydroxylapatite (CaHA; Radiesse, BioForm Medical, San Mateo, CA). Anesthetic is added to the compound prior to injection, resulting in a homogenous admixture of CaHA and anesthetic. A bolus of the mixture is injected into the skin, using tenting, and then spread throughout the hand. The result of this approach - mixing anesthetic with CaHA - is treatment that is easier to massage and disseminate, less painful to the patient than conventional hand injection, and characterized by less swelling and bruising, with minimal post-treatment downtime.

Childhood accidents: the relationship of family size to incidence, supervision, and rapidity of seeking medical care.

BACKGROUND: Large family size may be a risk factor for childhood accidents. A possible association with quality of child supervision and rapidity of seeking medical care has not been fully evaluated. OBJECTIVES: To determine whether children with multiple siblings are at increased risk for accidents, to assess whether quality of child supervision varies with family size, and to evaluate the relationship of family size with the rapidity of seeking medical care after an accident. METHODS: We prospectively studied 333 childhood accidents treated at TEREM (emergency care station) or the Shaare Zedek Medical Center. Details on family composition and the accident were obtained through parental interview. Family size of the study population was compared with that of the Jerusalem population. Families with one to three children (Group 1) and four or more children (Group 2) were compared with regard to type of supervision and different "Gap times" - the time interval from when the accident occurred until medical assistance was sought ("Gap 1"), the time from that medical contact until arrival at Shaare Zedek ("Gap 2"), and the time from the accident until arrival at Shaare Zedek for those children for whom interim medical assistance either was ("Gap 3A") or was not ("Gap 3B") sought. RESULTS: Children from families with 1, 2, 3, 4 and > or =5 children comprised 7.2%, 18.3%, 14.4%, 18.6% and 41.4% of our sample compared to 20.4%, 21.8%, 18.4%, 14.7% and 24.7% in the general population respectively. Children from Group 2 were less often attended to by an adult (44.5% vs. 62.0%) and more often were in the presence only of other children at the time of the accident (27.0% vs. 10.5%). Gaps 1, 2 and 3A in Group 2 (6.3 hours, 16.5 hours, 27.8 hours respectively) were longer than for Group 1 (2.7, 10.7, 13.3 hours respectively). CONCLUSIONS: The risk for accidents is increased among children from families with four or more children. The adequacy of child supervision in large families is impaired. There is a relative delay from the time of the accident until these children are brought for treatment.

Extending stochastic resonance for neuron models to general Lévy noise.

A recent paper by Patel and Kosko (2008) demonstrated stochastic resonance (SR) for general feedback continuous and spiking neuron models using additive Lévy noise constrained to have finite second moments. In this brief, we drop this constraint and show that their result extends to general LEvy noise models. We achieve this by showing that "large jump" discontinuities in the noise can be controlled so as to allow the stochastic model to tend to a deterministic one as the noise dissipates to zero. SR then follows by a "forbidden intervals" theorem as in Patel and Kosko's paper.