Utilization of the Free Fibular Flap for First Metatarsal Reconstruction.

Beyond being aesthetically unpleasing, metatarsal defects have been known to lead to several patient concerns such as intermetatarsal malpositioning and metatarsalgia. There are several reconstructive techniques that have been utilized for reconstruction of bony defects in the foot, including the free dorsal toe flap and dorsal metatarsal perforator flap. Our institution has utilized the free fibular flap for surgical management pertaining to tarsal reconstruction. Our study looks to evaluate the work of a single plastic surgeon and identify patient postoperative outcomes. A retrospective chart review was conducted at Beaumont Health System, Royal Oak for patients who underwent first metatarsal reconstruction with a free fibular flap between the years 2015 and 2022. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively gathered and analyzed. A total of two patients were isolated after chart review. Both patients were found to have tolerated the procedure well and had no intraoperative complications. In addition, all patients had clinically viable flaps and were satisfied with their surgical results. The free fibular flap may be used effectively in the management of metatarsal defects that have failed prior therapy. In our study, both patients who underwent surgical management with a free fibular flap were noted to have successful long-term results. With the right expertise and patient population, a free fibular flap can be highly successful in the repair of metatarsal defects.

Outcomes of Closed versus Open Rhinoplasty: A Systematic Review.

Open and closed rhinoplasty are two main approaches to perform nasal modifications. According to current literature, there is no current consensus among plastic surgeons and otolaryngologists on which technique is preferred in terms of aesthetic result, complications, and patient satisfaction. This study uses published research to determine whether open or closed rhinoplasty leads to superior patient outcomes. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews were followed and a literature search was conducted in four databases based on our search strategy. Articles were then imported into COVIDENCE where they underwent primary screening and full-text review. Twenty articles were selected in this study after 243 articles were screened. There were 4 case series, 12 retrospective cohort studies, 1 prospective cohort study, 1 case-control, and 2 outcomes research. There were three cosmetic studies, eight functional studies, and nine studies that included both cosmetic and functional components. Sixteen studies utilized both open and closed rhinoplasty and four utilized open rhinoplasty. Both techniques demonstrated high patient and provider satisfaction and no advantage was found between techniques. Based on available studies, we cannot conclude if there is a preference between open or closed rhinoplasty in terms of which technique leads to better patient outcomes. Several studies determined that open rhinoplasty and closed rhinoplasty leads to comparative patient satisfaction. To make outcome reporting more reliable and uniform among studies, authors should look to utilize the Nasal Obstruction and Septoplasty Effectiveness scale and the Rhinoplasty Outcome Evaluation.

Simultaneous Contralateral Autologous Breast Augmentation during Unilateral Breast Reconstruction Utilizing Deep Inferior Epigastric Flaps.

It is predicted that 281,550 new cases of invasive breast cancer and 49,290 new cases of ductal carcinoma in situ will be diagnosed this year. In this study, we will detail our experience with simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral deep inferior epigastric perforator (DIEP) flaps. Methods: A retrospective analysis of patients who underwent simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral DIEP flaps by the senior surgeons at Beaumont Health Systems, Royal Oak, was conducted. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively analyzed. Results: Seven patients who met the inclusion criteria were identified. One patient underwent immediate reconstruction with DIEP flaps, one patient had a history of lumpectomy and underwent delayed partial breast reconstruction, three patients had delayed unilateral DIEP breast reconstruction with contralateral breast augmentation, and two patients had previous augmentations that were revised. All patients examined in this review tolerated the procedures well and had clinically viable flaps along with superior aesthetic outcomes. Conclusions: This technique can be applied to various clinical conditions, including immediate breast reconstruction, delayed breast reconstruction, and salvage for failed implant-based reconstruction, leading to optimal patient outcomes and satisfaction. Unilateral breast reconstruction with simultaneous contralateral autologous breast augmentation utilizing bilateral DIEP flaps is a surgical technique that more plastic surgeons should utilize.

Comprehensive Treatment and Reconstructive Algorithm for Functional Restoration after Ballistic Facial Injury.

Background: Ballistic facial injuries are rare, with most trauma centers reporting 1-20 cases annually. These patients present significant management challenges to reconstructive surgeons, not only due to their rarity but also due to the complex decision-making process that is involved. The aim of this study was to review our experience with the application of craniofacial microsurgery in management of facial gunshot wounds. Methods: A retrospective review of a single-surgeon experience at a level I trauma center from 2011 to 2020 for patients sustaining self-inflicted gunshot wounds to the face requiring microsurgical reconstruction was performed. Outcomes included reconstructive techniques, free flap type and indication, airway evolution, feeding modality, respective timing of interventions, and complications. Results: Between 2012 and 2021, 13 patients presented for microsurgical reconstruction at our institution for gunshot wounds to the face. The majority (90%) of patients were men, and the average age at time of injury was 26. The median from the time of injury to first free flap was 93 days. Thirteen patients represented 23 free flaps. On average, patients underwent a total of two free flaps. The most common microsurgical flap was the fibula flap (14) followed by the radial forearm flap (6). Conclusions: Based on our findings, we describe a novel algorithm for function restoration and aesthetic revisions based on injury location. Underlying principles include avoiding early use of reconstruction plates, establishing occlusion early, and aligning bony segments using external fixation. An algorithmic approach to these injuries can improve outcomes.

Medial Canthus Reconstruction with the Paramedian Forehead Flap.

Background: The medial canthus represents the medial confluence of the upper and lower eyelid margins and plays an integral role in the lacrimal duct system. Various flaps have been utilized for the reconstruction of the lower eyelid in the medial canthal region. Our institution primarily utilizes the paramedian forehead flap for the reconstruction of medial canthus defects. Our study looked to evaluate the work of a single plastic surgeon and identify their postoperative outcomes. Methods: A retrospective chart review was conducted at Beaumont Health System, Royal Oak, for patients who underwent medial canthal repair by the lead surgeon between the years 2014 and 2018. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively gathered and analyzed. Results: A total of five patients were isolated. Patients underwent paramedian forehead flap medial canthal repair by the lead surgeon and were found to tolerate the procedure well. All patients had clinically viable flaps with aesthetically pleasing results. Conclusions: Utilization of the paramedian forehead flap leads to successful medial canthal repair with adequate coverage. Although the paramedian forehead flap requires three stages to complete, the procedure leaves patients with aesthetically pleasing results. In addition, the paramedian forehead flap has limited cases of ectropion. With the right expertise and patient population, the paramedian forehead flap can be highly successful in the repair of medial canthal defects.

Utilization of a Chimeric Medial Femoral Condyle Free Flap for Mandibular Osteoradionecrosis.

Background: Primary options for oromandibular reconstruction with osteocutaneous free flaps are the vascularized fibula and iliac crest. Complications of mandible reconstruction are not uncommon and include osteomyelitis, malunion, and osteoradionecrosis (ORN) after radiation therapy. The medial femoral condyle (MFC) free flap is an established salvage option for carpal reconstruction in hand surgery, frequently used for scaphoid nonunion and avascular necrosis. We hypothesize that the MFC flap can be utilized to restore blood supply and reverse the negative effects of radiotherapy in patients who require mandibular reconstruction due to ORN. Methods: A retrospective chart review was conducted at Beaumont Health System, Royal Oak, for patients who underwent MFC free flap reconstruction for mandibular ORN between the years 2012 and 2018. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively gathered. Results: A total of four patients were isolated. Four patients developed ORN after resection of squamous cell carcinoma and adjuvant radiotherapy. No patients experienced donor site deficits. Revisions after MFC reconstruction were dependent on individual aesthetics and involvement of neighboring tissue. All four patients continue to be followed with no current issues to the osseous component of the MFC flap. Conclusion: Utilization of the MFC periosteal flap is a viable option in selected patients to salvage nonunion/resorption of mandible reconstruction and ORN of the mandible. Our experience found that the MFC is able to provide pain resolution and healing of intraoral soft tissue defects, and may halt the progression of ORN of the mandible.

Outcomes Associated with Nasal Reconstruction Post-Rhinectomy: A Narrative Review.

The face and the external nose define an individual's physical appearance. Nasal deformities can cause facial disfigurement along with unwanted psychological repercussions. Nasal deformities range in severity, with the most severe cases being indications for a rhinectomy, due to the complexity of the nasal defect. According to published literature, there is no consensus among otolaryngologists and plastic surgeons on which technique or flap use is preferred in terms of complications, aesthetic outcome, or patient satisfaction. The goal of this study is to provide a comprehensive analysis of published studies on nasal reconstruction following rhinectomy. Using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines for writing systematic reviews, a systematic review was conducted. Four databases were searched using a search strategy. These articles were then imported into the COVIDENCE software and went screening and thorough article review. After screening 2,237 articles, 23 studies were then extracted for data collection analysis. We collected data from 12 case series, 4 case studies, 1 prospective case series, and 4 retrospective chart review studies. The most commonly reported flaps were forehead flaps, superior extended nasal myocutaneous island, forearm free flaps, anterolateral thigh (ALT) free flap, medial femoral condyle free flap ( n = 8), and zygomaticus implants ( n = 6), and retained nasal prosthesis. Although not specifically indicated by a certain number, the most common indication for the rhinectomy was malignancy, followed by traumas, postsurgical complications, radionecrosis, and congenital nasal malformations. Although several donor flaps can be used after rhinectomy, we conclude that there is no preference over what flap has superior patient outcomes after analysis. As of current, there are no prospective studies that exist. Therefore, more research is necessary to determine the results of each flap.

Eyelid Reanimation with Free Platysma Graft: Final Stage of Reconstruction after Gunshot Wound to Face.

Patients with gunshot wounds to the face have massive soft tissue and bony damage from projectile and blast injuries. They often require multiple, staged reconstructive surgeries with cross-facial nerve grafting and free muscle flap for re-establishment of facial expression. Injury to or total loss of the facial nerve and branches can result in loss of function of the orbicularis oculi muscle, which leads to the loss of protective mechanisms of eyelid function and blink reflex. The purpose of this article is to provide a literature review and discussion of eyelid reanimation after facial paralysis and to discuss our surgical technique with free platysma muscle grafts of the eyelid. The patient is a 45-year-old man with a history of a gunshot wound to the right face. He underwent multiple reconstructive surgeries in the past, and in preparation for eyelid reanimation, he underwent a cross-facial nerve graft from the left temporal branch to the right eyelid. At initial postoperative evaluation, the patient was able to close his right eye with minimal lagophthalmos, and at 3-month follow-up, he exhibited stronger blinking reflex. This case demonstrates that a free platysma graft with direct neurotization with cross-facial nerve graft fascicles can be utilized for restoration of spontaneous eyelid animation. However, there may be failure of neurotization and inability of the spontaneous blink reflex to be present. Despite these limitations, we still recommend the utilization of free platysma graft to provide upper eyelid reanimation through cross-facial nerve graft.

May-Thurner Syndrome and Lymphedema Reconstruction.

May-Thurner syndrome (MTS) is an anatomical variant that results in compression of the left common iliac vein by the right common iliac artery. Although often asymptomatic, lower extremity swelling/edema, deep venous thrombosis, post-thrombotic syndrome, and eventual lymphedema (due to long-standing venous obstruction) can develop. The clinical management of patients presenting for lymphedema surgery with concomitant or undiagnosed MTS is not well described. Methods: This review investigates two patients who were evaluated for unilateral lower extremity lymphedema, both of whom were subsequently diagnosed with MTS. Standard imaging (including lymphoscintigraphy, indocyanine green lymphangiography, and magnetic resonance venography) were performed to identify proximal venous obstruction. Treatment was accomplished using vascular surgical management, including stenting of the iliac vein before lymphedema reconstruction with vascularized lymph node transfer and multiple lymphovenous bypass. Results: Both patients we examined in this review had improvement of lymphedema with vascular surgical management. Literature review reveals that MTS has an incidence as high as 20% in the population, although commonly unidentified due to lack of symptomatology. Conclusions: There are no studies documenting the incidence of MTS in patients referred for lymphedema surgical management. Routine studies should be obtained to screen for proximal venous obstruction in patients presenting for surgical management of lower extremity lymphedema. Additional research is needed regarding the approach to managing patients with both MTS and lymphedema. Careful observational and prospective studies may elucidate the appropriate time interval between venous stenting and lymphedema microsurgical reconstruction.

An Unoperated Crouzon Family Treated with Monobloc Distraction: Challenges and Lessons.

Crouzon syndrome (CS) is a rare form of craniosynostosis characterized by bicoronal craniosynostosis and facial features including severe midface hypoplasia, exophthalmos, and hypertelorism. Most patients are diagnosed and treated in early childhood; however, there are a few reports of Crouzon patients treated as adults with monobloc facial advancement. To our knowledge, this is the first report of a family affected by CS treated sequentially with monobloc facial advancement using combined internal and external distraction osteogenesis (rigid external distraction). METHODS: We present a family from Jamaica (mother 47 years old, older daughter 17, and younger daughter 9) who were brought to our craniofacial clinic with stigmata of CS and no previous surgical intervention. Patients had bicoronal craniosynostosis and exorbitism, with varying severity, sequelae, and comorbidities. Here, we delineate our technique of monobloc distraction osteogenesis with advancement osteotomies using dual "push-pull" method, elevation of a split anteriorly based tunneled pericranial flap to seal off nasal cavity, and internal and external distraction. RESULTS: Our patients had favorable outcomes after reconstruction to reduce ocular symptoms and improve midface hypoplasia and aesthetic appearance. No intracranial injury, hardware/soft-tissue infection, hardware failure, or (new) loss of vision were encountered in 10 months follow-up. CONCLUSIONS: Dual "push-pull" monobloc distraction is safe and effective for a range of ages in CS; it allows good vector control, accommodates patient compliance, and allows early rigid external distraction device removal with sufficient time for consolidation. This surgery can be performed with highly satisfactory results.

Hypothenar hammer syndrome and repair of ulnar artery aneurysm in a patient without history of trauma.

The patient is a 50-year-old male with a history of tobacco use presented for evaluation of pulsatile right-hand mass. The patient was employed as a barber but had no known history of trauma or injury. He was diagnosed with hypothenar hammer syndrome and underwent excision of ulnar artery aneurysm with reconstruction of ulnar artery with interposition saphenous vein graft. The presented case describes an uncommon presentation of hypothenar hammer syndrome in a patient without history of repetitive blunt trauma or injury and discusses the diagnosis, pathophysiology and treatment options for symptomatic ulnar artery aneurysm.

Functional trait sorting increases over succession in metacommunity mosaics of fish assemblages.

Metacommunity theory predicts that the relative importance of regional and local processes structuring communities will change over time since initiation of community assembly. Determining effects of these processes on species and trait diversity over succession remains largely unaddressed in metacommunity ecology to date, yet could confer an improved mechanistic understanding of community assembly. To test theoretical predictions of the increasing importance of local processes in structuring communities over successional stages in metacommunities, we evaluated fish species and trait diversity in three pond metacommunities undergoing secondary succession from beaver (Castor canadensis) disturbance. Processes influencing taxonomic and trait diversity were contrasted across pond communities of different ages and in reference streams. Counter to predictions, the local environment became less important in structuring communities over succession but did exert a stronger effect on trait sorting. Beta diversity and trait richness declined over succession while there was no influence on species richness or trait dispersion. The trait filtering in older habitats was likely a response to the larger and deeper pond ecosystems characteristic of late succession. In contrast to these observed effects in ponds, the local environment primarily structured species and trait diversity in streams. Analyses of the relative importance of regional and local processes in structuring fish assemblages within each pond metacommunity suggests that habitat age and connectivity were more important than the environment in structuring communities but contributions were region and scale-dependent. Together, these findings highlight that regional and local processes can differentially influence taxonomic and trait diversity in successional metacommunity mosaics.

Total scrotal reconstruction following Fournier's gangrene with bilateral prelaminated superior medial thigh flaps.

The patient is a 45-year-old man diagnosed with Fournier's gangrene and underwent treatment for septic shock, broad-spectrum antibiotic therapy and extensive surgical debridement of perineum, including total scrotectomy, ischiorectal fossa, abdomen and left superior thigh and flank. The patient required multiple staged complex reconstruction of the scrotum utilising prelaminated superior medial thigh flaps with use of dermal matrix, split-thickness skin grafting and pedicled gracilis muscle flap for coverage of the ischiorectal wound. The patient had full recovery and followed up 1 year postoperatively. This report discusses our technique for total scrotal reconstruction and provides review of surgical reconstructive techniques for wounds due to Fournier's gangrene.

Palliative Reconstructive Surgery for Advanced Maxillofacial Osteosarcoma in the Peak of COVID-19 Pandemic: A Matter of Ethical Decision-making.

The coronavirus disease 2019 posed an unprecedented strain to plastic surgery services. The scarcity of validated guidelines-at the beginning of this healthcare crisis-to direct clinical, ethical, transparent decision-making for head and neck cancer patients requiring palliative reconstructive surgery was a difficult situation. We report a 15-year-old girl with an advanced chemoresistant rare radiotherapy-induced mandibular osteosarcoma during the early phase of the pandemic in the United States in mid-March 2020, when official recommendations for triage were still developing. Local guidelines suggested canceling all elective procedures, and allowed operating emergency and/or nonelective cases only. Many surgeons declined surgery due to patient's poor prognosis and high perioperative risk, but her mother pursued different professional opinions elsewhere. However, upon Beaumont hospital approval, the patient underwent radical en bloc resection of the tumor, hemimandibulectomy, zygomatic resection, maxillectomy, and hemipalate resection followed by reconstruction with free fibula osteocutaneous and anterolateral thigh flaps. The challenging decision to proceed with surgery was based on evidence-based and objective risk-stratifying scores, available at the time, and ethical recommendations from emerging reliable published literature. Despite a favorable postoperative outcome, the patient expired due to cardiac complications of the disease. Our patient taught us that ethical decision-making, sound clinical judgment, and a patient-centered individualized approach remain pivotal aspects of the medical profession. Although the surgery will not provide a cure for the disease, we have found that palliative reconstructive surgery can greatly improve patient's quality of life, and help family cope with the advancing stages of disease.

Intraneural Lipoma of the Digital Nerve: A Case Report and Literature Review.

Intraneural lipomas are rare soft-tissue tumors that can occur particularly within the median nerve. Even fewer cases have been reported of their occurrence within the ulnar nerve. These masses can cause compression neuropathies. In this report, we present the first documented case of an intraneural lipoma of an ulnar digital nerve.

Examining coastal dynamics and recreational water quality by quantifying multiple sewage specific markers in a North Carolina estuary.

Fecal contamination is observed downstream of municipal separate storm sewer systems in coastal North Carolina. While it is well accepted that wet weather contributes to this phenomenon, less is understood about the contribution of the complex hydrology in this low-lying coastal plain. A quantitative microbial assessment was conducted in Beaufort, North Carolina to identify trends and potential sources of fecal contamination in stormwater receiving waters. Fecal indicator concentrations were significantly higher in receiving water downstream of a tidally submerged outfall compared to an outfall that was permanently submerged (p < 0.001), though tidal height was not predictive of human-specific microbial source tracking (MST) marker concentrations at the tidally submerged site. Short-term rainfall (i.e. <12 h) was predictive of E. coli, Enterococcus spp., and human-specific MST marker concentrations (Fecal Bacteroides, BacHum, and HF183) in receiving waters. The strong correlation between 12-hr antecedent rainfall and Enterococcus spp. (r = 0.57, p < 0.001, n = 92) suggests a predictive model could be developed based on rainfall to communicate risk for bathers. Additional molecular marker data indicates that the delivery of fecal sources is complex and highly variable, likely due to the influence of tidal influx (saltwater intrusion from the estuary) into the low-lying stormwater pipes. In particular, elevated MST marker concentrations (up to 2.56 × 104 gene copies HF183/mL) were observed in standing water near surcharging street storm drain. These data are being used to establish a baseline for stormwater dynamics prior to dramatic rainfall in 2018 and to characterize the interaction between complex stormwater dynamics and water quality impairment in coastal NC.

Drought timing and local climate determine the sensitivity of eastern temperate forests to drought.

Projected changes in temperature and drought regime are likely to reduce carbon (C) storage in forests, thereby amplifying rates of climate change. While such reductions are often presumed to be greatest in semi-arid forests that experience widespread tree mortality, the consequences of drought may also be important in temperate mesic forests of Eastern North America (ENA) if tree growth is significantly curtailed by drought. Investigations of the environmental conditions that determine drought sensitivity are critically needed to accurately predict ecosystem feedbacks to climate change. We matched site factors with the growth responses to drought of 10,753 trees across mesic forests of ENA, representing 24 species and 346 stands, to determine the broad-scale drivers of drought sensitivity for the dominant trees in ENA. Here we show that two factors-the timing of drought, and the atmospheric demand for water (i.e., local potential evapotranspiration; PET)-are stronger drivers of drought sensitivity than soil and stand characteristics. Drought-induced reductions in tree growth were greatest when the droughts occurred during early-season peaks in radial growth, especially for trees growing in the warmest, driest regions (i.e., highest PET). Further, mean species trait values (rooting depth and ψ50 ) were poor predictors of drought sensitivity, as intraspecific variation in sensitivity was equal to or greater than interspecific variation in 17 of 24 species. From a general circulation model ensemble, we find that future increases in early-season PET may exacerbate these effects, and potentially offset gains in C uptake and storage in ENA owing to other global change factors.

Inhibition of fibroblasts reduced head and neck cancer growth by targeting fibroblast growth factor receptor.

OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCC) is a complex disease process involving interactions with carcinoma-associated fibroblasts and endothelial cells. We further investigated these relationships by suppressing stromal cell growth through the inhibition of fibroblast growth factor receptor (FGFR). STUDY DESIGN: Preclinical investigation. METHODS: HNSCC cell lines (FADU, OSC19, Cal27, SCC1, SCC5, SCC22A), fibroblast (HS27), and endothelial cells (human umbilical vascular endothelial cell) were cultured individually or in coculture. Proliferation was assessed following treatment with a range of physiologic concentrations of FGFR inhibitor PD173074. Mice bearing established HNSCC xenografts were treated with PD173074 (12 mg/kg), and tumor histology was analyzed for stromal composition, proliferation (Ki67 staining), and apoptosis (TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling] staining). RESULTS: In vitro, inhibition of FGFR with PD173074 dramatically reduced proliferation of fibroblasts and endothelial cells compared to untreated controls. However, HNSCC cell proliferation was not affected by inhibition of FGFR. When cocultured with fibroblasts, HNSCC cells proliferation increased by 15% to 80% (P < .01). Furthermore, this fibroblast-enhanced tumor cell growth was suppressed by FGFR inhibition. Additionally, treatment of mice bearing HNSCC xenografts with PD173074 resulted in significant growth inhibition (P < .001). Additionally, those tumors from mice treated with PD173074 had a smaller stromal component, decreased proliferation, and increased apoptosis. CONCLUSIONS: Targeting the FGFR pathway in head and neck cancer acts through the stromal components to decrease HNSCC growth in vivo and in vitro.

Modeling, synthesis and biological evaluation of potential retinoid X receptor (RXR) selective agonists: novel analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene).

This report describes the synthesis of analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), commonly known as bexarotene, and their analysis in acting as retinoid X receptor (RXR)-specific agonists. Compound 1 has FDA approval to treat cutaneous T-cell lymphoma (CTCL); however, its use can cause side effects such as hypothyroidism and increased triglyceride concentrations, presumably by disruption of RXR heterodimerization with other nuclear receptors. The novel analogues in the present study have been evaluated for RXR activation in an RXR mammalian-2-hybrid assay as well as an RXRE-mediated transcriptional assay and for their ability to induce apoptosis as well as for their mutagenicity and cytotoxicity. Analysis of 11 novel compounds revealed the discovery of three analogues that best induce RXR-mediated transcriptional activity, stimulate apoptosis, have comparable K(i) and EC(50) values to 1, and are selective RXR agonists. Our experimental approach suggests that rational drug design can develop new rexinoids with improved biological properties.