Hair-bearing human skin generated entirely from pluripotent stem cells.

The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor ß (TGFß) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are 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 the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto 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 that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.

Adverse effect of demineralized bone powder on osteogenesis of human mesenchymal stem cells.

Demineralized bone powder (DBP) has been used by clinicians for years to treat bone defects. Although DBP treatment often leads to successful bone healing, a number of studies using DBP have demonstrated poor bone formation. It is known that soluble factors released from DBP modulate bone formation. We hypothesized that DBP releases or interacts with soluble factors that modulate osteogenesis of mesenchymal stem cells (MSCs). Our in vitro study demonstrated that the expression of mRNA transcripts of bone-related markers decreased in osteogenic culture of human MSCs (hMSCs) with DBP compared to that without DBP. Using a high-throughput protein array, we identified insulin-like growth factor binding protein-1, thrombospondin, and angiostatin that were found abundant in the medium cultured with DBP. Separately, we detected a significant reduction of soluble calcium and phosphate in the DBP-present medium compared to that in the DBP-absent medium, and showed that hMSC osteogenesis was regulated by the amounts of soluble calcium and phosphate in the medium. Moreover, DBP was shown to sequester soluble calcium and phosphate in the medium, thereby depleting them from interacting with hMSCs during osteogenesis. This study provides a possible explanation to an important question associated with the use of DBP in clinical treatments.

Functional Outcomes After Transoral Plus Lateral Pharyngotomy Approach for Advanced Oral and Oropharyngeal Tumors.

Objective: The aim of this study was to evaluate our institutional experience with the combined transoral plus lateral pharyngotomy (TO+LP) approach in a subset of patients with advanced or recurrent oral and oropharyngeal malignancy. Study Design: A retrospective study of procedures utilizing TO+LP for cancer resection between January 2007 and July 2019. Setting: Tertiary academic medical center. Methods: Thirty-one patients underwent a TO+LP approach for the resection of oral and oropharyngeal tumors. Functional and oncologic outcomes were analyzed. Results: Eighteen (58.1%) patients were treated with TO+LP for recurrent disease. Twenty-nine required free tissue transfer and 2 (6.5%) had positive margins. The median time to decannulation was 22 days (range 6-100 days). Thirteen (41.9%) patients still required enteral feeding at their most recent follow-up. Patients without a history of prior radiation were decannulated sooner (p = .009) and were less likely to require enteral feeding at the first postoperative follow-up (p = .034) than those who had prior head and neck radiotherapy. Conclusion: A TO+LP approach can be used to achieve good functional and oncologic results for selected patients with advanced or recurrent oral and oropharyngeal cancer when minimally invasive options such as transoral robotic surgery, transoral laser microsurgery, or radiotherapy are not possible.

The radial forearm snake flap: An underutilized technique for fasciocutaneous and osteocutaneous forearm flaps with primary closure.

BACKGROUND: The radial forearm free flap (RFFF) is associated with troublesome donor site morbidity related to split thickness skin grafting (STSG). The radial forearm snake flap with primary closure of the donor site may reduce donor site complications. METHODS: Single institution, retrospective cohort study comparing rates of delayed donor site wound healing and tendon exposure in 52 patients undergoing radial forearm snake flap and 95 patients undergoing conventional RFFF with STSG closure of the donor site. RESULTS: Tendon exposure occurred in zero (0%) patients undergoing snake flap and four (4.2%) patients undergoing conventional RFFF (0/52 vs. 4/95; p = 0.297). Delayed wound healing occurred in zero (0%) patients undergoing snake flap and 19 (20.0%) patients undergoing conventional RFFF (0/52 vs. 19/95; p < 0.001). CONCLUSIONS: The radial forearm snake flap provides an alternative to conventional RFFF harvest, which enables primary donor site closure with reduced rates of delayed donor site healing.

Intraoperative ketorolac for pediatric tonsillectomy: Effect on post-tonsillectomy hemorrhage and perioperative analgesia.

OBJECTIVE: Determine the impact of ketorolac on post-tonsillectomy hemorrhage (PTH) and narcotic administration in children undergoing tonsillectomy. METHODS: Retrospective case series from 2013 to 2017. Patients younger than 18 years undergoing tonsillectomy were included. PTH was the primary outcome measured. Secondary measures include percentage of patients requiring surgical intervention for PTH, average time to PTH, the number of post-operative opioid doses, and average post-operative opioid dose. Statistical methods include Chi-square, Wilcoxon rank sum, and binary logistic regression analyses. RESULTS: During the study period, 669 patients received a single intraoperative dose of ketorolac (K+) and 653 patients did not receive ketorolac (K-). No differences were found in the rate of PTH (K- 6.5% vs. K+ 5.3%, RR = 0.82, 95% CI = 0.53 to 1.29, p = 0.40), surgical control of PTH (K- 4.0% vs. K+ 3.5%, RR = 0.87, CI = 0.51 to 1.51, p = 0.62), or average time [SD] to PTH (K- 6.0 [4.2] vs. K+ 5.2 [4.9] days; difference = 0.8 days; 95% CI, -1.3 to 2.9; p = 0.45). K+ patients had fewer post-operative opioid doses [SD] (K- 1.86 [1.14] vs. K+ 1.59 [1.23]; difference = -0.27; 95% CI, -0.053 to -0.49, Cohen d = 0.23) and a lower average opioid dose [SD] (K- 0.041 [0.032] vs. K+ 0.035 [0.030] mg/kg; difference = -0.006 mg/kg; 95% CI, -0.0003 to -0.012; Cohen d = 0.19). CONCLUSION: Ketorolac did not increase risk of hemorrhage following tonsillectomy and decreased narcotic use.

Immunosuppression Impact on Head and Neck Cutaneous Squamous Cell Carcinoma: A Systematic Review with Meta-analysis.

OBJECTIVE: The primary objective was to define and quantify the relationship between immunosuppression and prognosis in patients with cutaneous squamous cell carcinoma of the head and neck. DATA SOURCES: Ovid/Medline, PubMed, Embase, and Scopus were searched from inception through June 5, 2017, with cross-referenced subject headings of squamous cell carcinoma, skin neoplasms, head and neck neoplasms, and prognosis. Additional gray literature was queried. REVIEW METHODS: All prospective, retrospective, and cohort studies in the English literature investigating prognosis in patients with head and neck cutaneous squamous cell carcinoma were eligible for inclusion. Meta-analysis data were pooled using the fixed-effects model. The main outcome measures were hazard ratios detailing subgroup analysis between immunosuppressed and immunocompetent patients. RESULTS: Seventeen studies were eligible for inclusion; 317 of the 2886 patients were immunosuppressed. Meta-analysis with pooled hazard ratios was performed for all outcome variables with at least 3 reported hazard ratios. Immunosuppression portended a worse prognosis across all outcome variables of interest: locoregional recurrence (2.20; 95% confidence interval [CI], 1.45-3.36), disease-free survival (2.69; 95% CI, 1.60-4.51), disease-specific survival (3.61; 95% CI, 2.63-4.95), and overall survival (2.09; 95% CI, 1.64-2.67). CONCLUSION: This is the largest investigation into the impact of immunosuppression on head and neck cutaneous squamous cell carcinoma. Immunosuppressed patients experience worse recurrence and survival outcomes compared to immunocompetent counterparts. The data support formal inclusion of immunosuppression in head and neck cutaneous squamous cell carcinoma staging systems.

Metastatic synovial sarcoma of the scalp: Case report.

BACKGROUND: Synovial sarcoma is a malignant tumor of soft tissue that is rarely found in the head and neck. Even less common are metastasis within the head and neck. METHODS: We describe a case of a delayed metastatic synovial sarcoma to the scalp. A man who had been diagnosed and treated 16 years previously for monophasic synovial sarcoma of the groin, presented with a new scalp lesion confirmed to be metastatic monophasic synovial sarcoma. Wide local excision and sentinel lymph node biopsy (SLNB) were performed and adjuvant radiation therapy was deferred. RESULTS: A positron emission tomography (PET)/CT was obtained 3 months after surgery and showed no evidence of local recurrence or metastatic disease. CONCLUSION: This case report describes a rare case of synovial sarcoma metastasizing to the scalp. The genetic, histopathologic, and clinical features of synovial sarcoma are reviewed with a focus on their manifestation and management within the head and neck.