A Soft Skin Adhesive (SSA) Patch for Extended Release of Pirfenidone in Burn Wounds.

As much as half or more of deep partial-thickness burn wounds develop hypertrophic scarring and contracture. Once formed, treatments are only minimally effective. Pirfenidone (Pf), indicated for treatment of idiopathic pulmonary fibrosis, is an anti-inflammatory and anti-fibrotic small molecule that potentially can be repurposed as a preventative against scarring in burn wounds. We present a drug-in-matrix patch with a soft skin adhesive (SSA) wound-contacting layer for multi-day drug delivery of Pf into burn wounds at the point of injury. Our patch construction consists of an SSA adhesive layer (Liveo™ MG7-9850, Dupont, Wilmington, DE, USA) for wound fixation, an acrylic co-polymer drug matrix (DURO-TAK 87-2852, Henkel, Düsseldorf, Germany) as the drug (Pf) reservoir, and an outermost protective polyurethane backing. By employing a drug-in-matrix patch design, Pf can be loaded as high as 2 mg/cm2. Compared to the acrylic co-polymer adhesive patch preparations and commercial films, adding an SSA layer markedly reduces skin stripping observed under scanning electron microscopy (SEM). Moreover, the addition of varying SSA thicknesses did not interfere with the in vitro release kinetics or drug permeation in ex vivo porcine skin. The Pf patch can be easily applied onto and removed from deep partial-thickness burn wounds on Duroc pigs. Continuous multi-day dosing of Pf by the patches (>200 µg/cm2/day) reduced proinflammatory biomarkers in porcine burn wounds. Pf patches produced by the manual laboratory-scale process showed excellent stability, maintaining intact physical patch properties and in vitro biological activity for up to one year under long-term (25 °C at 60% RH) and 6 months under accelerated (40 °C at 75% RH) test conditions. To manufacture our wound safe-and-extended-release patch, we present scale-up processes using a machine-driven automated roll-to-roll pilot scale coater.

Comparative Transcriptome Analysis of Superficial and Deep Partial-Thickness Burn Wounds in Yorkshire vs Red Duroc Pigs.

Hypertrophic scars are a common negative outcome of deep partial-thickness (DPT) burn wounds resulting in increased dermal thickness, wound area contracture, and inflammation of the affected area. The red Duroc and Yorkshire porcine breeds are common large animal models for studying dermal wounds due to their structural similarities to human skin; however, the porcine transcriptomic profiles of dermal burn wounds and healing process are not well known. In response, a longitudinal transcriptomic comparative study was conducted comparing red Duroc and Yorkshire superficial and DPT burn wounds to their respective control uninjured tissue. Using next-generation RNA sequencing, total RNAs were isolated from burn wound tissue harvested on 0, 3, 7, 15, 30, and 60 days postburn, and mRNA-seq and gene expression read counts were generated. Significant differentially expressed genes relative to uninjured tissue were defined, and active biological processes were determined using gene set enrichment analyses. Additionally, collagen deposition, α-smooth muscle actin (SMA) protein concentration, epidermal and dermal thickness measurements, and wound area changes in response to burn injury were characterized. Overall, the red Duroc pigs, in response to both burn wound types, elicited a more robust and prolonged inflammatory immune response, fibroblast migration, and proliferation, as well as heightened levels of extracellular matrix modulation relative to respective burn types in the Yorkshire pigs. Collectively, the red Duroc DPT burn wounds produce a greater degree of hypertrophic scar-like response compared with Yorkshire DPT burn wounds. These findings will facilitate future porcine burn studies down-selecting treatment targets and determining the effects of novel therapeutic strategies.

T3SS and alginate biosynthesis of Pseudomonas aeruginosa impair healing of infected rabbit wounds.

Pseudomonas aeruginosa (a Gram-negative bacterium) is an opportunistic pathogen found in many infected wounds and is known to impair healing. To test the hypothesis that knocking out P. aeruginosa genes that are overexpressed during wound infection can cripple a pathogen's ability to impair healing, we assessed two pathways: the Type III secretion system (T3SS) and alginate biosynthesis. We generated single- and double-mutant strains of ExsA (T3SS activator), AlgD (GDP- mannose 6-dehydrogenase of alginate biosynthesis) and their complemented strains and evaluated their pathogenicity in a rabbit ear full-thickness excision-wound infection model. Wounds were inoculated with different strains (wild type, mutants, and complementary strains) at 106 CFU/wound on post-wounding day 3. After 24 h, 5 days and 9 days post-infection, wounds were harvested for measuring bacterial counts (viable and total) and wound healing (epithelial gap). On day 9 post-infection, the viable counts of the double mutant, (exsA/algD)‾ were 100-fold lower than the counts of the wild type (PAO1), single mutants, or the complement double-mutant, (exsA/algD)‾/+. Also, when compared to wounds infected with wild type or control strains, wounds infected with the double-knockout mutant was less inhibitory to wound healing (p < 0.05). Additionally, the double mutant showed greater susceptibility to macrophage phagocytosis in vitro than all other strains (p < 0.001). In conclusion, compared to single gene knockouts, double knockout of virulence genes in T3SS pathway and alginate biosynthesis pathway is more effective in reducing P. aeruginosa pathogenicity and its ability to impair wound healing. This study highlights the necessity of a dual-targeted anti-virulence strategy to improve healing outcomes of P. aeruginosa-infected wounds.

Temporal shifts in the mycobiome structure and network architecture associated with a rat (Rattus norvegicus) deep partial-thickness cutaneous burn.

With a diverse physiological interface to colonize, mammalian skin is the first line of defense against pathogen invasion and harbors a consortium of microbes integral in maintenance of epithelial barrier function and disease prevention. While the dynamic roles of skin bacterial residents are expansively studied, contributions of fungal constituents, the mycobiome, are largely overlooked. As a result, their influence during skin injury, such as disruption of skin integrity in burn injury and impairment of host immune defense system, is not clearly delineated. Burn patients experience a high risk of developing hard-to-treat fungal infections in comparison to other hospitalized patients. To discern the changes in the mycobiome profile and network assembly during cutaneous burn-injury, a rat scald burn model was used to survey the mycobiome in healthy (n = 30) (sham-burned) and burned (n = 24) skin over an 11-day period. The healthy skin demonstrated inter-animal heterogeneity over time, while the burned skin mycobiome transitioned toward a temporally stabile community with declining inter-animal variation starting at day 3 post-burn injury. Driven primarily by a significant increase in relative abundance of Candida, fungal species richness and abundance of the burned skin decreased, especially in days 7 and 11 post-burn. The network architecture of rat skin mycobiome displayed community reorganization toward increased network fragility and decreased stability compared to the healthy rat skin fungal network. This study provides the first account of the dynamic diversity observed in the rat skin mycobiome composition, structure, and network assembly associated with postcutaneous burn injury.

Identification of Metagenomics Structure and Function Associated With Temporal Changes in Rat (Rattus norvegicus) Skin Microbiome During Health and Cutaneous Burn.

The cutaneous skin microbiome is host to a vast ensemble of resident microbes that provide essential capabilities including protection of skin barrier integrity and modulation of the host immune response. Cutaneous burn-injury promotes alteration of cutaneous and systemic immune response that can affect both commensal and pathogenic microbes. A cross-sectional study of a limited number of burn patients revealed a difference in the bacteriome of burned versus control participants. Temporal changes of the skin microbiome during health and cutaneous burn-injury remains largely unknown. Furthermore, how this microbial shift relates to community function in the collective metagenome remain elusive. Due to cost considerations and reduced healing time, rodents are frequently used in burn research, despite inherent physiological differences between rodents and human skin. Using a rat burn model, a longitudinal study was conducted to characterize the rat skin bacterial residents and associated community functions in states of health (n = 30) (sham-burned) and when compromised by burn-injury (n = 24). To address the knowledge gap, traumatic thermal injury and disruption of cutaneous surface is associated with genus-level changes in the microbiota, reduced bacterial richness, and altered representation of bacterial genes and associated predicted functions across different skin microbial communities. These findings demonstrate that, upon burn-injury, there is a shift in diversity of the skin's organismal assemblages, yielding a core microbiome that is distinct at the genome and functional level. Moreover, deviations from the core community correlate with temporal changes post-injury and community transition from the state of cutaneous health to disease (burn-injury).

Intratracheal Inoculation of Fischer 344 Rats with Francisella tularensis.

Pulmonary infection with the bacterium Francisella tularensis can lead to the serious and potentially fatal disease, tularemia, in humans. Due to the current lack of an approved tularemia vaccine for humans, research is focused on vaccine development utilizing appropriate animal models. The Fischer 344 rat has emerged as a model that reflects human susceptibility to F. tularensis infection, and thus is an attractive model for tularemia vaccine development. Intratracheal inoculation of the Fischer 344 rat with F. tularensis mimics pulmonary exposure in humans. The successful delivery into the rat trachea is critical for pulmonary delivery. A laryngoscope with illumination is used to properly intubate the tracheae of anesthetized rats; the correct placement within the trachea is determined by a simple device to detect breathing. Following intubation, the F. tularensis culture is delivered in a measured dose via syringe. This technique standardizes pulmonary delivery of F. tularensis within the rat trachea to evaluate vaccine efficacy.

Closed traumatic rupture of the thenar muscles from the origin: a case report and review of the literature.

Closed traumatic rupture of the thenar muscles is an unusual and rare injury. Traumatic musculotendinous injuries in the hand and wrist occur primarily from penetrating trauma. Only 2 such cases were identified in medical literature. We report a case of closed traumatic rupture of the thenar muscles in an otherwise healthy 33-year-old female nurse who sustained a hyperabduction injury of her right thumb and wrist during a daily occupational routine, resulting in complete avulsion of the right abductor pollicis brevis and opponens pollicis from their origins. After declining initial surgical management, the patient subsequently returned 6 months later reporting continued pain, paresthesias, and thenar deformation, and requested surgical intervention. On examination, she continued to exhibit weakness of thumb abduction and mild weakness with opposition. She was again offered an open carpal tunnel release with exploration of the thenar eminence and possible tendon transfer, although she adamantly refused any tendon transfer. An open right carpal tunnel release was performed with exploration and direct muscle repair through a lateral thenar incision. Primary muscular reattachment was accomplished by suturing the abductor pollicis brevis and opponens pollicis to the flexor retinaculum and the trapezium. Functional results 15 months after surgery were satisfactory with improvements in abduction and opposition of the thumb and restoration of the thenar contour. The chosen surgical technique for repair resulted in good functional outcome, while avoiding the need for tendon transfer.

Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD) protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP). The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

The incidence of acute traumatic tendon injuries in the hand and wrist: a 10-year population-based study.

BACKGROUND: Acute traumatic tendon injuries of the hand and wrist are commonly encountered in the emergency department. Despite the frequency, few studies have examined the true incidence of acute traumatic tendon injuries in the hand and wrist or compared the incidences of both extensor and flexor tendon injuries. METHODS: We performed a retrospective population-based cohort study of all acute traumatic tendon injuries of the hand and wrist in a mixed urban and rural Midwest county in the United States between 2001-2010. A regional epidemiologic database and medical codes were used to identify index cases. Epidemiologic information including occupation, year of injury, mechanism of injury and the injured tendon and zone were recorded. RESULTS: During the 10-year study period there was an incidence rate of 33.2 injuries per 100,000 person-years. There was a decreasing rate of injury during the study period. Highest incidence of injury occurred at 20-29 years of age. There was significant association between injury rate and age, and males had a higher incidence than females. The majority of cases involved a single tendon, with extensor tendon injuries occurring more frequently than flexor tendons. Typically, extensor tendon injuries involved zone three of the index finger, while flexor tendons involved zone two of the index finger. Work-related injuries accounted for 24.9% of acute traumatic tendon injuries. The occupations of work-related injuries were assigned to major groups defined by the 2010 Standard Occupational Classification structure. After assigning these patients' occupations to respective major groups, the most common groups work-related injuries occurred in construction and extraction occupations (44.2%), food preparation and serving related occupations (14.4%), and transportation and material moving occupations (12.5%). CONCLUSIONS: Epidemiology data enhances our knowledge of injury patterns and may play a role in the prevention and treatment of future injuries, with an end result of reducing lost work time and economic burden.

Lipidation of the FPI protein IglE contributes to Francisella tularensis ssp. novicida intramacrophage replication and virulence.

Francisella tularensis is a Gram-negative bacterium responsible for the human disease tularemia. The Francisella pathogenicity island (FPI) encodes a secretion system related to type VI secretion systems (T6SS) which allows F. tularensis to escape the phagosome and replicate within the cytosol of infected macrophages and ultimately cause disease. A lipoprotein is typically found encoded within T6SS gene clusters and is believed to anchor portions of the secretion apparatus to the outer membrane. We show that the FPI protein IglE is a lipoprotein that incorporates (3)H-palmitate and localizes to the outer membrane. A C22G IglE mutant failed to be lipidated and failed to localize to the outer membrane, consistent with C22 being the site of lipidation. Francisella tularensis ssp. novicida expressing IglE C22G is defective for replication in macrophages and unable to cause disease in mice. Bacterial two-hybrid analysis demonstrated that IglE interacts with the C-terminal portion of the FPI inner membrane protein PdpB, and PhoA fusion analysis indicated the PdpB C-terminus is located within the periplasm. We predict this interaction facilitates channel formation to allow secretion through this system.

Rare presentations of primary melanoma and special populations: a systematic review.

A subset of patients with melanoma present in rare and unique clinical circumstances requiring specific considerations with respect to diagnostic and therapeutic interventions. Herein, we present our review of patients with: (1) primary mucosal melanoma of the head and neck, gastrointestinal, and genitourinary tracts; (2) primary melanoma of the eye; (3) desmoplastic melanoma; (4) subungual melanoma; (5) melanoma in special populations: children, nonwhites, as well as a discussion of familial melanoma.

Surgical management of subungual melanoma: mayo clinic experience of 124 cases.

BACKGROUND: Optimal surgical management of subungual malignant melanoma (SMM) has been debated. METHODS: Our tumor registry was reviewed for surgically treated cases of SMM from 1914 to 2010. Resection levels were compared with outcome. RESULTS: During a 96-year period, 124 cases of SMM were identified (65 men and 59 women). Mean age at diagnosis was 58 years. Mean length of symptoms before diagnosis was 2.2 years. Lesions occurred on the hand (n = 79) and foot (n = 45). The thumb (33.8%) and hallux (25.0%) were affected most. At diagnosis, most had local (83.9%) and regional nodal involvement (12.9%). Mean follow-up was 9.4 years.Mean Breslow depth was 3.1 mm. Amputations were most commonly performed on the thumb at the proximal phalanx or metacarpophalangeal joint (43.9%), and on the hallux at the proximal phalanx or metatarsophalangeal joint (69.0%).Disease progression occurred in 61 (49.2%) patients, and most commonly occurred as regional nodal (62.3%) and distant metastasis (42.6%). Disease progression-free survival rates at 5, 10, and 15 years were 57.1%, 49.9%, and 47.0%, respectively. Fifty-three patients died of melanoma-related causes. Disease-specific survival rates at 5, 10, and 15 years after surgery were 59.3%, 49.3%, and 45.2%. Overall survival rates at 5, 10, and 15 years were 60.5%, 43.8%, and 33.1%.In 116 patients who underwent amputation, resection level outcome analysis with univariate and multivariate analysis adjusting for tumor depth and clinical involvement demonstrated that level of resection was not significantly associated with progression-free, overall, or disease-specific survival. CONCLUSIONS: Diagnosis of subungual melanoma is often delayed and carries a poor prognosis. Conservative resections are warranted as resection level does not influence outcome when histologically free margins are obtained. Amputation through the proximal phalanx or the metatarsophalangeal joint is required in the hallux and toes. Fingers require resection through the distal interphalangeal joint. For the thumb, although resection through the interphalangeal joint proved adequate, secondary efforts should be directed toward maximizing function and quality of life. Function-preserving resections in the thumb with nail removal, partial distal phalanx resection, and volar flap reconstruction are easily performed and preserve length, maximize joint and sensory function, and improve cosmesis.

Long-term satisfaction of reduction mammaplasty for bilateral symptomatic macromastia in younger patients.

PURPOSE: There is controversy about performing reduction mammaplasty in younger patients. Although no studies show poor surgical outcomes, a paucity of data exists on long-term outcomes and satisfaction. METHODS: A single center mixed-mode mail and telephone surveyed 203 women who underwent reduction mammaplasty for symptomatic macromastia between 1985 and 2005, who were <21 years of age at surgery. A total of 99 women responded (48.8%). RESULTS: Mean operative patient age was 19.1 years (range, 16.2-20.9 years). Mean follow-up was 15.6 years (range, 6.0-26.4 years). Sustained long-term symptom resolution was highest with shoulder pain (94.7%), breast pain (92.0%), and intertrigo (88.6%). Improvements in feeling uncomfortable (87.5%), finding clothes that fit (86.0%), sports participation (85.2%), and running (83.7%) were reported. Patients reported self-perceived decreased nipple sensitivity (67.2%) and difficulties breast-feeding (65.2%). Prominent incisional scarring was reported by 71.7%; however, 56.5% reported that scarring had not affected them in any way. The majority (93.9%) rated the overall success of their operation as at least 50% successful; 42.4% reported 100% success in treating the problems. Improved quality of life was reported by 88.7%. Most respondents (66.7%) would definitely recommend this procedure to a friend or family member at the same age. Knowing what they know now, 95.9% would choose to have the surgery again. Subgroup analysis of patients <18 years of age (n = 23; mean age, 17.3 years) at the time of surgery revealed equivalent results. CONCLUSIONS: Long-term follow-up of reduction mammaplasty in patients aged 16-20 years shows good overall satisfaction and improvements in quality of life.

Muscle hernias of the leg: A case report and comprehensive review of the literature.

A case involving a retired, elderly male war veteran with a symptomatic peroneus brevis muscle hernia causing superficial peroneal nerve compression with chosen surgical management is presented. Symptomatic muscle hernias of the extremities occur most commonly in the leg and are a rare cause of chronic leg pain. Historically, treating military surgeons pioneered the early documentation of leg hernias observed in active military recruits. A focal fascial defect can cause a muscle to herniate, forming a variable palpable subcutaneous mass, and causing pain and potentially neuropathic symptoms with nerve involvement. While the true incidence is not known, the etiology has been classified as secondary to a congenital (or constitutional) fascial weakness, or acquired fascial defect, usually secondary to direct or indirect trauma. The highest occurrence is believed to be in young, physically active males. Involvement of the tibialis anterior is most common, although other muscles have been reported. Dynamic ultrasonography or magnetic resonance imaging is often used to confirm diagnosis and guide treatment. Most symptomatic cases respond successfully to conservative treatment, with surgery reserved for refractory cases. A variety of surgical techniques have been described, ranging from fasciotomy to anatomical repair of the fascial defect, with no consensus on optimal treatment. Clinicians must remember to consider muscle hernias in their repertoire of differential diagnoses for chronic leg pain or neuropathy. A comprehensive review of muscle hernias of the leg is presented to highlight their history, occurrence, presentation, diagnosis and treatment.

Les auteurs présentent le cas d'un vétéran âgé retraité ayant une hernie symptomatique du muscle court péronier responsable d'une compression du nerf péronier superficiel associée à une intervention chirurgicale précise. Les hernies symptomatiques des muscles des membres se produisent surtout dans la jambe et constituent de rares causes de douleurs chroniques de la jambe. Par le passé, les chirurgiens militaires traitants ont consigné les premiers cas de hernies de la jambe observés chez les recrues militaires actives. Une anomalie aponévrotique focale peut provoquer la herniation d'un muscle, une masse sous-cutanée palpable entraînant de la douleur et des symptômes au potentiel neuropathique associés à une atteinte nerveuse. On n'en connaît pas la véritable incidence, mais l'étiologie est classée comme secondaire à une faiblesse aponévrotique congénitale (ou constitutionnelle) ou à une anomalie aponévrotique acquise, qui découle habituellement d'un traumatisme direct ou indirect. On pense que l'occurrence la plus élevée s'observe chez les jeunes hommes physiquement actifs. L'atteinte du muscle tibial antérieur est la plus courante, mais d'autres muscles peuvent être touchés. L'échographie dynamique ou l'imagerie par résonance magnétique permet souvent de confirmer le diagnostic et d'orienter le traitement. La plupart des cas symptomatiques répondent bien à un traitement prudent, la chirurgie étant réservée aux cas réfractaires. Il existe diverses techniques chirurgicales, de la fasciotomie à la réparation anatomique de l'anomalie aponévrotique, mais aucun consensus ne se dégage quant au traitement optimal. Les cliniciens doivent se souvenir d'envisager les hernies musculaires dans le diagnostic différentiel des douleurs chroniques ou des neuropathies de la jambe. Une analyse approfondie des hernies musculaires de la jambe est présentée afin d'en faire ressortir les antécédents, l'occurrence, la présentation, le diagnostic et le traitement.

A ventrally localized protease in the Drosophila egg controls embryo dorsoventral polarity.

Drosophila embryo dorsoventral (DV) polarity is defined by serine protease activity in the perivitelline space (PVS) between the embryonic membrane and the inner layer of the eggshell. Gastrulation Defective (GD) cleaves and activates Snake (Snk). Activated Snk cleaves and activates Easter (Ea), exclusively on the ventral side of the embryo. Activated Ea then processes Spätzle (Spz) into the activating ligand for Toll, a transmembrane receptor that is distributed throughout the embryonic plasma membrane. Ventral activation of Toll depends upon the activity of the Pipe sulfotransferase in the ventral region of the follicular epithelium that surrounds the developing oocyte. Pipe transfers sulfate residues to several protein components of the inner vitelline membrane layer of the eggshell. Here we show that GD protein becomes localized in the ventral PVS in a Pipe-dependent process. Moreover, ventrally concentrated GD acts to promote the cleavage of Ea by Snk through an extracatalytic mechanism that is distinct from GD's proteolytic activation of Snk. Together, these observations illuminate the mechanism through which spatially restricted sulfotransferase activity in the developing egg chamber leads to localization of serine protease activity and ultimately to spatially specific activation of the Toll receptor in the Drosophila embryo.

Localization and activation of the Drosophila protease easter require the ER-resident saposin-like protein seele.

Drosophila embryonic dorsal-ventral polarity is generated by a series of serine protease processing events in the egg perivitelline space. Gastrulation Defective processes Snake, which then cleaves Easter, which then processes Spätzle into the activating ligand for the Toll receptor. seele was identified in a screen for mutations that, when homozygous in ovarian germline clones, lead to the formation of progeny embryos with altered embryonic patterning; maternal loss of seele function leads to the production of moderately dorsalized embryos. By combining constitutively active versions of Gastrulation Defective, Snake, Easter, and Spätzle with loss-of-function alleles of seele, we find that Seele activity is dispensable for Spätzle-mediated activation of Toll but is required for Easter, Snake, and Gastrulation Defective to exert their effects on dorsal-ventral patterning. Moreover, Seele function is required specifically for secretion of Easter from the developing embryo into the perivitelline space and for Easter processing. Seele protein resides in the endoplasmic reticulum of blastoderm embryos, suggesting a role in the trafficking of Easter to the perivitelline space, prerequisite to its processing and function. Easter transport to the perivitelline space represents a previously unappreciated control point in the signal transduction pathway that controls Drosophila embryonic dorsal-ventral polarity.

Reduction mammaplasty: a review of managed care medical policy coverage criteria.

BACKGROUND: Insurance companies evaluate the medical necessity for breast reduction surgery based on internal company medical policies, but the correlation of insurance company criteria to the scientifically established indications for reduction mammaplasty has never been studied. The authors obtained 90 insurance company medical policies for reduction mammaplasty to determine whether the criteria on which coverage determinations are made are consistent with published data regarding the indications for this procedure. METHODS: The authors reviewed the medical literature on reduction mammaplasty and identified what conclusions can reasonably be drawn from this literature on the common insurance criteria used to determine medical necessity for reduction mammaplasty. Conclusions based on the medical literature regarding volume of reduction, symptom presentation, conservative therapy, obesity, presence of bra strap grooving and intertrigo, and age at time of reduction were formulated, and these conclusions were compared with the criteria of 90 different health insurance reduction mammaplasty medical policies. RESULTS: The authors were unable to identify any medical policies that could be supported in entirety by the medical literature and many that are completely unfounded based on the medical literature. CONCLUSIONS: Insurance company medical policy requirements with respect to reduction mammaplasty are, in many cases, arbitrary and without scientific basis. Requirements for a specific volume of reduction, a minimum age, a maximum body weight, and a trial of conservative therapy are required by the majority of managed care medical policies, even though scientific support for any of these requirements is not evident in the medical literature.