The skin is a multi-layered organ equipped with appendages (i.e. follicles and glands) critical for regulating bodily fluid retention and temperature, guarding against external stresses, and mediating touch and pain sensation 1 , 2 . Reconstruction of appendage-bearing skin in cultures and in bioengineered grafts remains an unmet biomedical challenge 3 – 9 . Here, we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use step-wise modulation of the TGFβ and FGF signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During 4–5 months incubation, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis, and pigmented hair follicles equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking human touch circuitry. Single-cell RNA-sequencing and direct comparison to foetal specimens suggest that skin organoids are equivalent to human facial skin in the second-trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted on nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo . We anticipate skin organoids will be foundational to future studies of human skin development, disease modelling, or reconstructive surgery.
Objective: Three-dimensional printing technology is being employed in a variety of medical and surgical specialties to improve patient care and advance resident physician training. As the costs of implementing three-dimensional printing have declined, the use of this technology has expanded, especially within surgical specialties. This article explores the types of threedimensional printing available, highlights the benefits and drawbacks of each methodology, provides examples of how three-dimensional printing has been applied within the field of otolaryngology -head and neck surgery, discusses future innovations, and explores the financial impact of these advances.Data Sources: Articles were identified from PubMed and Ovid Medline.Review Methods: PubMed and Ovid Medline were queried for English articles published between 2011and 2016, including a few articles prior to this time as relevant examples. Search terms included: three-dimensional printing, 3D-printing, otolaryngology, additive manufacturing, craniofacial, reconstruction, temporal bone, airway, sinus, cost, and anatomic models.Conclusions: Three-dimensional printing has been used in recent years in otolaryngology for preoperative planning, education, prostheses, grafting, and reconstruction. Emerging technologies include the printing of tissue scaffolds for the auricle and nose, more realistic training models, and personalized implantable medical devices. Implications for Practice:After accounting for the upfront costs of three-dimensional printing, its utilization in surgical models, patient-specific implants, and custom instruments can reduce operating room time and thus decrease costs. Educational and training models provide an opportunity to better visualize anomalies, practice surgical technique, predict problems that might arise, and improve quality by reducing mistakes.3
Objective After significant restrictions initially due to the COVID-19 pandemic, otolaryngologists have begun resuming normal clinical practice. However, the risk of SARS-CoV-2 transmission to health care workers through aerosolization and airborne transmission during rhinologic surgery remains incompletely characterized. The objective of this study was to quantify the number concentrations of aerosols generated during rhinologic surgery with and without interventions involving 3 passive suction devices. Study Design Cadaver simulation. Setting Dedicated surgical laboratory. Subjects and Methods In a simulation of rhinologic procedures with and without different passive suction interventions, the concentrations of generated aerosols in the particle size range of 0.30 to 10.0 µm were quantified with an optical particle sizer. Results Functional endoscopic sinus surgery with and without microdebrider, high-speed powered drilling, use of an ultrasonic aspirator, and electrocautery all produced statistically significant increases in concentrations of aerosols of various sizes ( P < .05). Powered drilling, ultrasonic aspirator, and electrocautery generated the highest concentration of aerosols, predominantly submicroparticles <1 µm. All interventions with a suction device were effective in reducing aerosols, though the surgical smoke evacuation system was the most effective passive suction method in 2 of the 5 surgical conditions with statistical significance ( P < .05). Conclusion Significant aerosol concentrations were produced in the range of 0.30 to 10.0 µm during all rhinologic procedures in this cadaver simulation. Rhinologic surgery with a passive suction device results in significant mitigation of generated aerosols.
The skin is important for regulating bodily fluid retention and temperature, 16 guarding against external stresses, and mediating touch and pain sensation. The skin 17 is also susceptible to damage from burns, diseases, or genetic defects, which affect 18 nearly one billion people worldwide 1,2 . For the advancement of skin regenerative 19 therapies, it remains challenging to construct new skin with hair follicles and nerves 20 in tissue cultures and in bioengineered skin grafts [3][4][5][6][7][8] . Here, we report an organoid culture system that generates complex skin from human pluripotent stem cells. We 1 use step-wise modulation of the TGFb and FGF signalling pathways to co-induce 2 cranial epithelial cells and neural crest cells within a spherical cell aggregate. During 3 4-5 months incubation, we observe the emergence of a cyst-like skin organoid 4 composed of stratified epidermis, fat-rich dermis, and pigmented hair follicles 5 equipped with sebaceous glands. A network of sensory neurons and Schwann cells 6 form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking 7 human touch circuitry. Single-cell RNA sequencing and direct comparison to foetal 8 specimens suggest that skin organoids are equivalent to human facial skin in the 9 second-trimester of development. Moreover, we show that skin organoids produce 10 planar hair-bearing skin when grafted on nude mice. Together, our results 11 demonstrate the self-assembly of nearly complete skin tissue in vitro that can be 12 used to reconstitute skin in vivo. We anticipate that our skin organoid model will be 13 foundational to future studies of human skin development, disease modelling, or 14 reconstructive surgery. 15 16For decades, culture systems containing epidermal and dermal cells have been used to 17 model human skin outside of the body 3,9,10 ; however, it has been persistently difficult to 18 grow and maintain functional skin appendages in culture. We recently reported that 19 appendage-bearing skin organoids can be generated via directed differentiation of 20 epidermal and dermal cells from mouse pluripotent stem cells (PSCs) 4 . From this study, we 21 recognised that a 3D cyst composed of surface ectoderm (i.e. epidermal precursors) 22 enveloped by mesenchymal cells (i.e. dermal precursors) creates a self-organizing system
To describe a technique for creation of a split calvarial bone L-shaped strut that provides dorsal support while increasing tip projection in patients with substantial septal saddle nose deformities from various underlying inflammatory conditions and surgical resection. Methods: Case series and review of the literature. Results: Fifteen patients underwent nasal reconstruction at our institution using the split calvarial bone Lshaped strut technique with postoperative follow-up to 36 months (range, 9-36 months). The causes of septal perforation leading to saddle nose deformity included cocaine use, infection, sarcoidosis, malignant lesion, iatrogenic causes, and Wegener granulomatosis. All cases resulted in an augmented, straightened nasal dorsum and increased tip projection. Results were maintained throughout follow-up with no evidence of graft infection, resorption, or migration. Conclusions: The split calvarial bone L-shaped strut provides dual benefits of dorsal support and increased tip projection. Numerous techniques have been discussed for dorsal augmentation with varied success; however, the long-term maintenance of this graft in patients with severely compromised vascularity owing to underlying inflammatory conditions such as Wegener granulomatosis highlights its presumed advantages. The procedure can be performed using the external rhinoplasty approach, obviating the need for radix incisions for plating or intranasal mucosal incisions. These advantages make the L-shaped strut technique excellent for nasal reconstruction in patients with substantial septal saddle nose deformities regardless of cause and duration of defect.
Background:The taboo of avoiding nonsteroidal antiinflammatory drugs (NSAIDs) a er functional endoscopic sinus surgery (FESS) has been waning. The impetus to reduce opioid prescriptions in view of the opioid epidemic led the authors to change their practices to include NSAIDs a er sinus surgery. This study's aim was to analyze the differences between patients before and a er we began recommending NSAIDs a er FESS. Methods:A prospective cohort study was performed on patients undergoing FESS or other endoscopic nasal surgeries at 3 institutions, by 5 rhinologists and 1 facial plastic surgeon. Before introducing NSAIDs, all patients were given a prescription for hydrocodone-acetaminophen 5/325 mg and also recommended preferentially to use acetaminophen 325 mg. A er the addition of NSAIDs, ibuprofen 200 mg and acetaminophen 325 mg were recommended preferentially, using the narcotic as a rescue medication. Patients kept a pain diary and medication log, and gave a visual analog scale (VAS) score for overall pain. Demographics, surgical variables, and comorbidities were also analyzed. Results:One hundred sixty-six total patients were recruited and had data that could be analyzed (65 without NSAIDs, 101 with NSAIDs). Overall, mean pain VAS score was 3.12 ± 1.95 for the non-NSAID group and 2.33 ± 2.30 for the NSAID group (p value = 0.006). The day with the highest mean pain was the first postoperative day. The mean number of total opioid pills taken was 6.94 ± 6.85 without NSAIDs vs 3.77 ± 4.56 with NSAIDs (p = 0.018). Age and gender were found to be the only consistently significant patient variables to affect pain. There were no bleeding complications.Conclusion: NSAID use was introduced into the practices of 5 practicing rhinologists and 1 facial plastic surgeon. No bleeding complications were seen. Both pain and overall opioid usage were reduced significantly. C 2019 ARS-AAOA, LLC.
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