Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

Clinical and Optical Coherence Tomography Correlation of Vascular Conditions Treated With a Novel, Variable-Sequenced, Long-Pulsed, 532 and 1,064 nm Laser With Cryogen Spray Cooling.

BACKGROUND: Patients frequently seek laser treatment for vascular conditions. More recently, a novel 532 and 1,064 nm laser was developed to offer greater flexibility. OBJECTIVE: A prospective clinical trial evaluated the safety and efficacy of a novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling (DermaV, Lutronic, South Korea). MATERIALS AND METHODS: Subjects with vascular conditions were enrolled for laser treatments. Clinical evaluations and optical coherence tomography (OCT) imaging were performed. RESULTS: Thirteen subjects were enrolled. The mean age was 51.3 years, and 92.3% were women. Fitzpatrick skin types I-IV were included. Treatment indications included broken blood vessels, rosacea, port-wine birthmark, and spider angioma. For physician investigator grading, all subjects were graded as improved at both 30-day and 90-day follow-up. Blinded photographic review by 3 independent, blinded physicians had a mean of 89.7% of cases selected correctly with at least 2 of 3 in agreement for 100.0% of cases. Optical coherence tomography imaging showed significant reductions in vessel density ( p = .018) and diameter ( p = .003) of the superficial vascular plexus. No serious adverse events occurred. CONCLUSION: A novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling can safely and effectively improve vascular conditions and lesions as determined by both clinical and OCT evaluation.

Paired Treatment Using Radiofrequency Microneedling and 755-nm Picosecond Laser With Fractionated Lens Array for Facial Rejuvenation.

BACKGROUND: Patients frequently complain about fine lines, wrinkles, dyschromia, and photoaging, for which lasers and energy-based devices can treat each of these. Pairing various devices in a single treatment session can be safe and effective, but different technologies, mechanisms, histologies, parameters, and techniques must be considered. OBJECTIVE: To examine the utility of a paired treatment regimen using radiofrequency microneedling and 755-nm picosecond laser with fractionated lens array to improve the clinical appearance of facial wrinkles and photoaging. MATERIALS AND METHODS: A prospective clinical study investigated this paired treatment regimen using 4 monthly sessions. RESULTS: Twenty-five subjects were enrolled, while 18 subjects completed 3-month follow-up. The mean age was 54 years, and 92% were women. Fitzpatrick Skin Types I to IV were represented. Assessments compared baseline with the 3-month follow-up. Two of 3 blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 94.4% of cases. For physician Global Aesthetic Improvement Scale, 100% of subjects had clinical improvement. Overall, 88.9% of subjects were considered to be satisfied with their treatment. No serious or unanticipated adverse events occurred. CONCLUSION: Paired treatment using radiofrequency microneedling and 755-nm picosecond laser with fractionated lens array can safely and effectively improve facial wrinkles and photoaging.

High-Intensity, High-Frequency, Parallel Ultrasound Beams for Cellulite of the Buttocks and Thighs.

BACKGROUND: Ultrasound energy can successfully treat fine lines and wrinkles, as well as lift the eyebrow and submentum. Ultrasound waves of high intensity induce thermal injury in the dermis with subsequent tissue remodeling. OBJECTIVE: To examine the utility of a novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams to improve the clinical appearance of cellulite on the thighs and buttocks. MATERIALS AND METHODS: A prospective, multicenter, clinical study investigated this novel ultrasound device using 2 treatments. RESULTS: Sixty-five subjects completed both treatments. The mean age was 46 years, and 100% were women. Fitzpatrick skin types I to VI were represented. Assessments compared 3-month follow-up with baseline. Two blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 89.2%. For Cellulite Severity Scale rating, there was significant improvement of 1.61 units (p < .001). For cellulite Global Aesthetic Improvement Scale (GAIS), 89.2% had improvement, with a mean of 0.87 units (p < .001). For Laxity Scale rating, there was significant improvement of 0.70 units (p < .001). For skin laxity GAIS, 89.2% had improvement, with a mean of 0.76 units (p < .001). No device-related adverse events occurred. CONCLUSION: A novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams can safely and effectively improve the clinical appearance of cellulite on the thighs and buttocks.

Extension Phase of a Multi-Center, Randomized, Blinded Clinical Study Evaluating the Efficacy and Safety of a Novel Topical Product for Facial Dyschromia.

BACKGROUND: Dyschromia can be associated with increased production and/or reduced clearance of pigmentation in the skin. Multiple pathways are involved in causality. A novel topical product was recently developed, which contains actives that have been validated through in-vitro and clinical studies to counteract pigmentation related to photodamage, PIH, and melasma. This study further evaluates the safety and efficacy of this product for facial dyschromia during an additional 3-month extension period following the completion of the previous 12-week multi-center trial.  Study Design: Subjects from the previous multi-center trial with mild to severe facial dyschromia at baseline were eligible to participate in this 3-month extension study upon completion of that trial. This extension study evaluated the continued use of the novel topical product with PATH-3 Technology (Alastin Skincare, Carlsbad, CA) over a 3-month period. Subjects who were previously randomized to the novel topical product continued using it and for those previously randomized to hydroquinone 4% discontinued its use. Both cohorts continued daily sunscreen use. Blinded investigators assessed subjects at follow-up visits at 16, 20, and 24 weeks. RESULTS: Twenty-six (26) subjects completed the extension phase of the pivotal trial, with 13 subjects in each of the AL and HQ-BREAK cohorts. Significant improvements were seen within the AL cohort from weeks 12 to 24 for facial dyschromia (P=0.0158) and skin tone/clarity/evenness (P=0.0067), while there were no significant improvements seen in the HQ-BREAK cohort. The HQ-BREAK cohort had more subjects who worsened with facial dyschromia and skin tone/clarity/evenness. For the mMASI, the HQ-BREAK cohort demonstrated regression at week 24 compared to week 12, while the AL cohort instead experienced continued improvement. This difference was found to be significant (P=0.02). No study-related adverse events were reported for either cohort.  Conclusion: A novel topical product designed to counteract various steps in pigmentation pathways using PATH-3 Technology has been demonstrated to be safe and effective in treating facial dyschromia on a long-term basis. In contrast to the significant rebound experienced by subjects with HQ, the AL cohort continued to demonstrate ongoing improvement. J Drugs Dermatol. 2024;23(1):1266-1270.     doi:10.36849/JDD.7622.

Progesterone from ovulatory menstrual cycles is an important cause of breast cancer.

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

The macrophage paradox.

Macrophages are a diverse population of phagocytic cells that reside in tissues throughout the body. At sites of infection, macrophages encounter and engulf invading microbes. Accordingly, macrophages possess specialized effector functions to kill or coordinate the elimination of their prey. Nevertheless, many intracellular bacterial pathogens preferentially replicate inside macrophages. Here we consider explanations for what we call "the macrophage paradox:" why do so many pathogenic bacteria replicate in the very cells equipped to destroy them? We ask whether replication in macrophages is an unavoidable fate that essentially defines a key requirement to be a pathogen. Conversely, we consider whether fundamental aspects of macrophage biology provide unique cellular or metabolic environments that pathogens can exploit. We conclude that resolution of the macrophage paradox requires acknowledgment of the richness and complexity of macrophages as a replicative niche.

Largest comparative analysis: Novel large spot size 595 nm, high-energy, pulsed dye laser reduces number of treatments for improvement of adult and pediatric port wine birthmarks.

OBJECTIVE: Port wine birthmarks (PWBs) are vascular malformations affecting 0.3%-0.5% of newborns with the tendency to persist into adulthood without adequate treatment of the heterogenous ectatic vessels. This study compares treatment outcomes and parameters of the prior generation pulsed dye laser (PPDL) and the larger spot novel generation pulsed dye laser (NPDL) to establish whether a larger spot size laser provides greater clearance with fewer treatments. METHODS: One hundred and sixty patients were treated with either the PPDL (80 patients) and NPDL (80 patients) with retrospective review of age, body site, laser treatment parameters, number of treatments, and improvement following laser therapy. RESULTS: Patients treated with PPDL were older on average than patients treated with NPDL (mean 24.8 ± 19.7 vs. mean 17.1± 19.3 years, p < 0.05). The majority of lesions treated with PPDL were located on the face and neck, whereas truncal and extremity sites were more frequently treated with the NPDL. Use of NPDL was associated with a mean maximum spot size of 13.1 mm and mean maximum fluence of 7.3 J/cm2 with pulse durations of 0.45-3 ms, whereas use of the PPDL was associated with a mean spot size of 10.8 mm and mean maximum fluence of 8.8 J/cm2 with pulse durations of 0.45-6 ms. Fifty percent improvement was seen with 8.8 PPDL treatments compared to 4.3 NPDL treatments (p ≤ 0.01) with no significant difference in overall mean improvement between both devices at the chosen parameters. Multiple regression analysis showed that device type, not age or lesion location, was the only statistically significant independent variable to affect the endpoint of at least 50% improvement of the lesion. CONCLUSIONS: Use of the larger spot NPDL is associated with achieving 50% improvement with fewer treatments.

Prospective Evaluation of the Safety and Efficacy of Thermomechanical Fractional Injury for Perioral Rhytides.

BACKGROUND: Perioral rhytides can be treated with laser and energy-based devices. More recently, a novel fractional thermomechanical skin rejuvenation system was developed to cause controlled thermal injury through direct heat transfer. OBJECTIVE: A prospective clinical trial evaluated the safety and efficacy of a thermomechanical fractional injury device (Tixel 2, Novoxel, Netanya, Israel) for perioral rhytides. MATERIALS AND METHODS: Subjects with moderate-to-severe perioral rhytides were enrolled and underwent 4 monthly treatments. RESULTS: Twenty-three subjects were enrolled and completed all study visits. Mean age was 62.5 years, and 100.0% were women. Fitzpatrick Skin Types I-IV were included. For Fitzpatrick Wrinkle Classification System (FWCS), mean baseline score was 6.9. Per investigator, there was a mean 1.9-grade improvement in FWCS at 3-month follow-up ( p < .0001). At 3-month follow-up, 8.7% (n = 2) of subjects had a 3-grade improvement, 69.6% (n = 16) had a 2-grade improvement, and 21.7% (n = 5) had a 1-grade improvement. For physician Global Aesthetics Improvement Scale at 3-month follow-up, 69.6% (n = 16) had 76% to 100% improvement, 13.0% (n = 3) had 51% to 75% improvement, and 17.4% (n = 4) had 26% to 50% improvement. There were no severe adverse events, and subjects experienced minimal pain. CONCLUSION: A novel device using thermomechanical fractional injury was demonstrated to be safe and effective in the treatment of perioral rhytides.

Safety and Efficacy of a Thermomechanical Fractional Injury Device for Periorbital Rhytides.

BACKGROUND: Periorbital rejuvenation is a common cosmetic concern. A fractional thermomechanical skin rejuvenation system was developed to offer clinical improvements from direct heat transfer. OBJECTIVE: A prospective study evaluated the efficacy and safety of the device for periorbital fine lines and wrinkles. MATERIALS AND METHODS: Subjects with moderate-to-severe periorbital rhytides were enrolled and underwent 4 monthly treatments with a novel device using thermomechanical fractional injury (Tixel 2; Novoxel, Netanya, Israel). RESULTS: Fifty-one subjects were enrolled. Mean age was 56.8 years, and 88.2% were women. Fitzpatrick skin Types I to IV were included. For Fitzpatrick Wrinkle Classification System (FWCS), mean baseline score was 5.7. Per investigator, there was a mean 2.0-grade improvement in FWCS at 3-month follow-up ( p < .0001). Per 3 blinded physician raters, there was a mean improvement of 2.2 ( p < .0001), 2.0 ( p < .0001), and 1.2 ( p < .0001) in FWCS at 3-month follow-up. Each of the raters correctly identified posttreatment images for 87.5%, 77.1%, and 75.0% of subjects. At least 2 raters agreed on grading 83.3% of subjects as responders. There were no severe adverse events. Subjects experienced minimal pain and downtime. CONCLUSION: A novel device using thermomechanical fractional injury was demonstrated to be safe and effective in the treatment of periorbital rhytides.

Safety and Efficacy of a Novel, Variable-Sequenced, Long-Pulsed, 532-nm and 1,064-nm Laser With Cryogen Spray Cooling for Pigmented and Vascular Lesions.

BACKGROUND: Patients frequently seek treatment for vascular and pigmented lesions. More recently, a novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling was developed to offer greater flexibility in treatments. OBJECTIVE: A prospective clinical trial evaluated the safety and efficacy of a novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling (DermaV, Lutronic, South Korea). MATERIALS AND METHODS: Subjects with vascular and/or pigmented lesions were enrolled and underwent laser treatments. RESULTS: Twenty-three subjects were enrolled with vascular lesions (39.1%), pigmented lesions (17.4%), and both (43.5%). Mean age was 53.1 years, and 91.3% were women. Fitzpatrick skin types II-IV were included. All subjects were treated with 532 nm, and 4 were also treated with 1,064 nm. According to 4 blinded physician reviewers, correct before and after photographs were selected in 94.7%, 92.1%, 84.2%, and 76.3% of cases. Overall, 86.8% were responders, meaning that at least 3 of 4 reviewers agreed. For Global Aesthetic Improvement Scale, improvement occurred in 81.6%, 81.6%, 81.6%, and 76.3% of cases. No serious adverse events occurred. Overall, 87.0% of subjects reported being very satisfied or satisfied. CONCLUSION: A novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling can safely and effectively improve vascular and pigmented lesions.

Analysis of port-wine birthmark vascular characteristics by location: Utility of optical coherence tomography mapping.

INTRODUCTION: Port-wine birthmarks (PWBs) are congenital capillary malformations that can be located on any area of the body. Vascular features include vessel size, depth, and density, which can greatly differ between patients, individual lesions, and even sites within the same lesion. Previous studies have determined that the location of PWB lesions has impacted their clinical response to laser treatment. OBJECTIVE: We utilized dynamic optical coherence tomography (D-OCT) to measure in vivo vessel diameter, density, and superficial plexus depth in patients of all ages with PWB on various sites of the body. We hypothesized that these vascular characteristics would differ according to body location. MATERIALS AND METHODS: Patients who had a PWB and presented to clinic at three sites for treatment with the pulsed dye laser (PDL) were enrolled into the study. A D-OCT scanner was utilized for noninvasive, in vivo imaging of PWB lesions. The depth of the top portion of the superficial vascular plexus was estimated as the depth at which the vessel density reaches 50% of the maximum. Vessel diameter and density were calculated by incorporated software algorithm. RESULTS: A total of 108 patients were enrolled into the study. There was a total of 204 measurements of PWB lesions. Of all patients, 56.5% (n = 61) reported having a previous treatment with PDL. Of all D-OCT scans, 62.3% (n = 127) were located on the head, 14.2% (n = 29) the upper extremities, 8.3% (n = 17) the lower extremities, 7.8% (n = 16) the trunk, and 7.8% (n = 15) the neck. All locations were compared for each vascular characteristic. For superficial plexus depth, lesions on the head were significantly shallower than those on the upper extremities (217 vs. 284 µm; p < 0.001) and lower extremities (217 vs. 309 µm; p < 0.001). For vessel diameter, lesions on the head had significantly larger vessels than those on the upper extremities (100 vs. 72 µm; p = 0.001). For vessel density, lesions on the head had significantly denser vessels than those on the trunk (19% vs. 9.6%; p = 0.039) and upper extremities (19% vs. 9.3%; p < 0.001) CONCLUSIONS: PWB lesions have distinct vascular characteristics, which can be associated with their body location. This includes superficial vascular plexus depth as well as vessel diameter and density.

Evaluation of Device-Based Cutaneous Channels Using Optical Coherence Tomography: Impact for Topical Drug Delivery.

BACKGROUND: Topical medications play a large role in the management of cutaneous diseases, but penetration is limited. Device-assisted drug delivery using mechanical destruction, lasers, and other energy-based modalities can increase penetration and absorption through creation of transcutaneous channels. OBJECTIVE: To examine real-time, in vivo cutaneous changes in response to various devices used to improve topical drug delivery through optical coherence tomography (OCT) imaging. METHODS AND MATERIALS: Treatment was performed with 8 medical devices, including mechanical destruction, lasers, and other energy-based modalities. Optical coherence tomography was used for real-time, noninvasive, in vivo imaging. RESULTS: Using OCT, microneedling and radiofrequency microneedling demonstrated no cutaneous channels. Both low-energy, low-density, fractional nonablative lasers produced transient channels, which closed within hours. The fractional nonablative 1,927-nm thulium fiber and 1,550-nm erbium fiber lasers created channels with epidermal debris within, which were still closing at 24 hours. The fractional thermomechanical ablative device and the fractional ablative CO2 laser produced channels that were still open at 24 hours. CO2 laser channels had thick rims of coagulated tissue and remained open for longer. CONCLUSION: Demonstrable differences among the devices were seen, and only some can produce observable channels, the characteristics of which vary with each technology.

Quantifying Skin Uptake of Topicals After 1,927-nm and 1,440-nm Nonablative Fractional Diode Laser Treatment.

BACKGROUND: Although the stratum corneum limits transdermal absorption of topicals, laser devices can enhance topical uptake by disrupting the skin barrier. Nonablative lasers are commonly used, but their effects on topical uptake should be quantified to optimize outcomes. OBJECTIVE: The objective of this study is to analyze transdermal uptake of 4 topicals after nonablative fractional diode laser pretreatment. METHODS AND MATERIALS: Human donor tissue was pretreated ex vivo with a nonablative fractional diode laser (1,927 nm or 1,440 nm, at varying treatment densities, powers, and peak energies) followed by application of either 2% salicylic acid, 10% ascorbic acid, over-the-counter mineral eye serum, or 4% hydroquinone. Topical uptake was quantified over 24 hours. RESULTS: Despite lower power settings, pretreatment with the 1,927 nm wavelength was associated with greater uptake of 10% ascorbic acid, mineral eye serum, and 4% hydroquinone than the 1,440 nm wavelength. In addition, 1,440-nm laser pretreatment with higher density (320 microscopic treatment zones [MTZ]/cm 2 ) and peak power (3 W) was associated with similar uptake but greater retention of 2% salicylic acid and greater uptake of 10% ascorbic acid than that with lower density (80 MTZ/cm 2 ) and peak power (1.2 W). CONCLUSION: When using laser pretreatment, device settings should be adjusted to balance outcomes with potential side effects.

Enhancing Skin Uptake of Topical Antioxidants With 1,440-nm Nonablative Fractional Diode Laser Pretreatment.

BACKGROUND: Energy-based devices, such as nonablative lasers, are a promising method to enhance the delivery and absorption of topically applied molecules. OBJECTIVE: To characterize ex vivo uptake of common antioxidant topicals after pretreatment with a nonablative laser wavelength. MATERIALS AND METHODS: Using donor human skin tissue, uptake of 3 topical antioxidants was analyzed (C E Ferulic with 15% l-ascorbic acid [15% vitamin C serum], Phloretin CF with ferulic acid [10% vitamin C serum], and Phyto+ [botanical serum]; SkinCeuticals, Dallas, TX; 2010 formulations) after pretreatment with a 1,440-nm nonablative fractional diode laser. RESULTS: Pretreatment with the 1,440-nm laser enhanced uptake of 15% and 10% vitamin C serums by approximately 10 and 21 times, respectively, compared to controls. Laser pretreatment also enhanced uptake of botanical serum by approximately 6 times relative to controls. Permeation of vitamin C and botanical serums was also enhanced through laser pretreatment. CONCLUSION: Nonablative laser pretreatment increased uptake and permeation of topical antioxidants. Optimizing treatment requires consideration of the device and treatment parameters as well as the properties of the topical formulation.

Enhanced Uptake and Retention of 0.03% Bimatoprost, 0.5% 5-Fluorouracil, and 5% Minoxidil After 1,550-nm or 1,927-nm Nonablative Laser Pretreatment.

BACKGROUND: Laser pretreatment with cosmeceutical topicals is growing in popularity. However, lasers may also enhance the uptake of medical topicals that treat dermatologic conditions, such as vitiligo, alopecia, and cancerous and precancerous lesions. Permeation of these topicals must be quantified to optimize treatment protocols. OBJECTIVE: To analyze transdermal uptake of 3 topicals after nonablative fractional 1,550-nm erbium-doped glass or 1,927-nm thulium fiber laser pretreatment. METHODS AND MATERIALS: Human donor tissue was pretreated with a nonablative fractional 1,550-nm erbium-doped glass or 1,927-nm thulium fiber laser followed by application of 0.03% bimatoprost, 0.5% 5-fluorouracil, or 5% minoxidil. Permeation and retention were measured over 24 hours (bimatoprost and 5-fluorouracil) or 90 minutes (minoxidil), and uptake was calculated. RESULTS: Pretreatment with 1,927-nm thulium laser (500 MTZ/cm2; 5 mJ; 5 W) enhanced uptake and retention of bimatoprost versus untreated control at 24 hours post-treatment. Pretreatment with 1,550-nm erbium-doped glass laser (2,000 MTZ/cm2; 10 mJ; 30 W) enhanced permeation, uptake, and retention of 5-fluorouracil at 24 hours post-treatment and enhanced permeation and uptake of minoxidil at 90 minutes post-treatment. CONCLUSION: Nonablative laser pretreatment may enhance topical treatment of dermatologic conditions. Device settings must be optimized to maximize topical permeation while minimizing laser-associated thermal side effects.

Boundary Conditions Matter-Impact of Test Setup on Inferred Construct Mechanics in Plated Distal Femur Osteotomies.

The mechanics of distal femur fracture fixation has been widely studied in bench tests that employ a variety of approaches for holding and constraining femurs to apply loads. No standard test methods have been adopted for these tests and the impact of test setup on inferred construct mechanics has not been reported. Accordingly, the purpose of this study was to use finite element models to compare the mechanical performance of a supracondylar osteotomy with lateral plating under conditions that replicate several common bench test methods. A literature review was used to define a parameterized virtual model of a plated distal femur osteotomy in axial compression loading with four boundary condition sets ranging from minimally to highly constrained. Axial stiffness, fracture gap closure, and transverse motion at the fracture line were recorded for a range of applied loads and bridge spans. The results showed that construct mechanical performance was highly sensitive to boundary conditions imposed by the mechanical test fixtures. Increasing the degrees of constraint, for example, by potting and rigidly clamping one or more ends of the specimen, caused up to a 25× increase in axial stiffness of the construct. Transverse motion and gap closure at the fracture line, which is an important driver of interfragmentary strain, was also largely influenced by the constraint test setup. These results suggest that caution should be used when comparing reported results between bench tests that use different fixtures and that standardization of testing methods is needed in this field.

Turning scientific serendipity into discoveries in breast cancer research and treatment: a tale of PhD students and a 50-year roaming tamoxifen team.

PURPOSE: This retrospective, about a single "mobile" laboratory in six locations on two continents, is intended as a case study in discovery for trainees and junior faculty in the medical sciences. Your knowledge of your topic is necessary to expect the unexpected. HISTORICAL METHOD: In 1972, there was no tamoxifen, only ICI 46, 474, a non-steroidal anti-estrogen with little chance of clinical development. No one would ever be foolish enough to predict that the medicine, 20 years later, would achieve legendary status as the first targeted treatment for breast cancer, and millions of women would benefit from long-term adjuvant tamoxifen therapy. The secret of tamoxifen's success was a translational research strategy proposed in the mid 1970's. This strategy was to treat only patients with estrogen receptor (ER)-positive breast cancer and deploy 5 or more years of adjuvant tamoxifen therapy to prevent recurrence. Additionally, tamoxifen prevented mammary cancer in animals. Could the medicine prevent breast cancer in women? RESULTS: Tamoxifen and the failed breast cancer drug raloxifene became the first selective estrogen receptor modulators (SERMs): a new drug group, discovered at the University of Wisconsin, Comprehensive Cancer Center. Serendipity can play a fundamental role in discovery, but there must be a rigorous preparation for the investigator to appreciate the possibility of a pending discovery. This article follows the unanticipated discoveries when PhD students "get the wrong answer." The secret of success of my six Tamoxifen Teams was their technical excellence to create models, to decipher mechanisms, that drove the development of new medicines. Discoveries are listed that either changed women's health or allowed an understanding of originally opaque mechanisms of action of potential therapies. These advances in women's health were supported entirely by government-sponsored peer-reviewed funding and major philanthropy from the Lynn Sage Breast Cancer Foundation, the Avon Foundation, and the Susan G. Komen Breast Cancer Foundation. The resulting lives saved or extended, families aided in a time of crisis and the injection of billions of dollars into national economies by drug development, is proof of the value of Federal or philanthropic investment into unencumbered research aimed at saving millions of lives.

Vascular characteristics of port wine birthmarks as measured by dynamic optical coherence tomography.

BACKGROUND: Port wine birthmarks (PWBs) are congenital capillary malformations. Vessel characteristics, such as diameter and depth, may impact presentation and outcomes. They can be imaged using dynamic optical coherence tomography, a high-resolution, noninvasive imaging method. PURPOSE: We conducted a cross-sectional observational study to measure in vivo vascular characteristics as a function of PWB color. METHODS: Patients undergoing treatment for PWB were recruited from 3 sites. PWBs were classified by color. Dynamic optical coherence tomography images with calculations were obtained. RESULTS: One hundred eight patients were enrolled. Mean age correlated with PWB color, with birthmarks being lighter in younger patients and darker in older patients (P < .01). Mean superficial plexus depth was significantly shallower in purple PWBs than in pink PWBs. Color was not associated with significant differences in mean superficial vessel density or diameter. Among pink PWBs, each 10-year increase in age was associated with a 10.6-µm increase in superficial plexus depth. Among purple PWBs, each 10-year increase in age was associated with a 16.2-µm reduction in superficial plexus depth. In lesions without prior treatment, vessel density was 12.7% lower in purple PWBs than in pink PWBs. CONCLUSION: Superficial vessels of purple PWBs were significantly closer to the epidermis than those of pink PWBs, which might impact optimal laser parameters.

Efficacy and Safety of High-Intensity, High-Frequency, Parallel Ultrasound Beams for Fine Lines and Wrinkles.

BACKGROUND: Ultrasound energy has been used for cutaneous rejuvenation, including treatment of fine lines and wrinkles. Ultrasound waves of high intensity can induce thermal injury in the dermis, which causes tissue coagulation and remodeling. OBJECTIVE: To examine the safety and utility of a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams to improve fine lines and wrinkles of the face and neck. MATERIALS AND METHODS: A prospective, multicenter, clinical study investigated the utility of this novel ultrasound device to improve fine lines and wrinkles. Sixty subjects were enrolled for single treatment to the face and neck. RESULTS: Fifty-eight subjects completed the study. The mean age was 58 years, and 87.9% were women. Fitzpatrick skin Types I to VI were represented. Assessments compared 12-week follow-up with baseline. Two blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 78% of subjects. There was significant improvement of 1 to 3 Fitzpatrick Wrinkle and Elastosis Scale units in 86% of subjects. For investigator global improvement scores, 88% of subjects had improvement. Overall, 72% of subjects noted improvement, and the majority were satisfied. There were no device-related adverse events. CONCLUSION: Treatment with a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams safely improved the clinical appearance of fine lines and wrinkles of the face and neck.