Citations

Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN + subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community.

Background: Multiple effective treatments exist for correction of skin photoaging. Topical L-ascorbic acid (vitamin C), a well-known antioxidant and topical human platelet extract (HPE), is a novel off-the-shelf cosmetic ingredient that has shown positive results in recent clinical studies. HPE is a leukocyte-depleted allogeneic product derived from United States–sourced, pooled, apheresed platelets produced with consistent batch quality, purity, and effect. The authors sought to characterize the effect of topical HPE (plated) intense serum (Rion Aesthetics) compared with vitamin C (C E Ferulic with 15% L-ascorbic acid; SkinCeuticals) in skin rejuvenation of dorsal hands after 12 to 26 weeks of twice-daily use. Methods: This prospective, longitudinal study sought to compare the effectiveness of 2 known treatments for skin rejuvenation. Evaluations at baseline and 6, 12, and 26 weeks included photographic documentation to assess common skin concerns related to aging. Results: For age-related skin appearance on the dorsal hands, topical HPE was noninferior to topical vitamin C for improvement in brown spot fractional area, wrinkle fractional area, and improvement in luminosity at 12 weeks after twice-daily topical use. Conclusions: HPE performed as well as vitamin C to rejuvenate the skin on the dorsal hands after 12 to 26 weeks of twice-daily topical use. Both topical serums may yield similar or superior results versus invasive procedures, such as intense pulsed light, in reducing brown spots on the dorsal hands. These topical products work equally well in both sexes. Skin improvements lasted through 6 months. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The digitization of medical records and expanding electronic health records has created an era of “Big Data” with an abundance of available information ranging from clinical notes to imaging studies. In the field of rheumatology, medical imaging is used to guide both diagnosis and treatment of a wide variety of rheumatic conditions. Although there is an abundance of data to analyze, traditional methods of image analysis are human resource intensive. Fortunately, the growth of artificial intelligence (AI) may be a solution to handle large datasets. In particular, computer vision is a field within AI that analyzes images and extracts information. Computer vision has impressive capabilities and can be applied to rheumatologic conditions, necessitating a need to understand how computer vision works. In this article, we provide an overview of AI in rheumatology and conclude with a five step process to plan and conduct research in the field of computer vision. The five steps include (1) project definition, (2) data handling, (3) model development, (4) performance evaluation, and (5) deployment into clinical care.

Abstract Background Massive modular endoprostheses have become a primary means of reconstruction after oncologic resection of a lower extremity tumor. These implants are commonly made with cobalt-chromium alloys that can undergo wear and corrosion, releasing cobalt and chromium ions into the surrounding tissue and blood. However, there are few studies about the blood metal levels in these patients. Question/purpose What is the whole blood cobalt and chromium ion level in patients with massive modular endoprostheses? Methods We performed a cross-sectional study of our total joints registry to identify patients with a history of an endoprosthetic reconstruction performed at our institution. Patients who were alive at the time of our review in addition to those undergoing an endoprosthetic reconstruction after an oncologic resection were included. Whole blood samples were obtained from 27 (14 male and 13 female) patients with a history of a lower extremity oncologic endoprosthesis. The median time from surgery to blood collection was 8 years (range 6 months to 32 years). Blood samples were collected and stored in metal-free ethylenediaminetetraacetic acid tubes. Samples were analyzed on an inductively coupled plasma mass spectrometer in an International Organization for Standardization seven-class clean room using polytetrafluoroethylene-coated instruments to reduce the risk of metal contamination. The analytical measuring range was 1 to 200 ng/mL for chromium and cobalt. Cobalt and chromium levels were considered elevated when the blood level was ≥ 1 ppb. Results Cobalt levels were elevated in 59% (16 of 27) of patients, and chromium levels were elevated in 26% (seven of 27). In patients with elevated metal ion values, 15 of 17 patients had a reconstruction using a Stryker/Howmedica Global Modular Replacement System implant. Conclusion Blood metal levels were elevated in patients who received reconstructions using modular oncology endoprostheses Future work is needed to establish appropriate follow-up routines and determine whether and when systemic complications occur because of elevated metal levels and how to potentially address these elevated levels when complications occur. Prospective and retrospective collaboration between multiple centers and specialty societies will be necessary to address these unknown questions in this potentially vulnerable patient group. Level of Evidence Level IV, therapeutic study.

Background: Removal of well-fixed femoral components during revision total hip arthroplasty (THA) can be difficult and time-consuming 1 , leading to numerous complications, such as femoral perforation, bone loss, and fracture. Extended trochanteric osteotomies (ETOs), which provide wide exposure and direct access to the femoral canal under controlled conditions, have become a popular method to circumvent these challenges. ETOs were popularized by Wagner (i.e., the anterior-based osteotomy), and later modified by Paprosky (i.e., the lateral-based osteotomy) 2 . Description: The decision to utilize the laterally based Paprosky ETO versus the anteriorly based Wagner ETO is primarily based on surgeon preference, the location and type of in situ implants, and the osseous anatomy. Typically, a laterally based ETO is most facile in conjunction with a posterior approach and an anteriorly based ETO is most commonly paired with a lateral or anterolateral approach. Attention must be paid to maintaining vascularity to the osteotomy fragment, including minimizing stripping of the vastus lateralis from the osteotomy fragment and maintaining abductor attachments to the osteotomy fragment. When utilizing a laterally based ETO, the posterior border of the vastus lateralis must be carefully elevated to provide exposure for performance of the osteotomy. When an anteriorly based osteotomy is performed, the surgeon may instead extend the abductor tenotomy proximally with use of a longitudinal split of the vastus lateralis distally, which helps to keep the anterior and posterior sleeves of soft tissue in continuity. In either approach, dissection of the vastus lateralis involves managing several large vascular perforators. We prefer performing careful blunt dissection to identify the perforators and prophylactically controlling them, with ligation of large vessels and electrocautery of smaller vessels. Vascular clips are also available in case difficult-to-control bleeding is encountered. In general, an oscillating saw (with preference for a thin blade) is utilized to complete the posterior longitudinal limb of the ETO, extending approximately 12 to 16 cm distally from the tip of the greater trochanter. Although a 12 to 16-cm zone is required to maintain maximum vascularity to the osteotomized fragment, the osteotomy length must ultimately be determined by (1) the length of the femoral component to be removed; (2) the presence of distal bone ingrowth, ongrowth, or cement; and (3) the presence of distal hardware or stemmed knee components. A smaller oscillating saw is then utilized to complete the transverse limb at the previously identified distal extent. A high-speed pencil-tip burr is utilized to complete the corners of the osteotomy in a rounded configuration, and a combination of saws and pencil-tip burrs is utilized to create partial proximal and distal anterior longitudinal limbs of the osteotomy to the extent allowed by the soft-tissue attachments. The anterior longitudinal limb may be further weakened in a controlled fashion with use of serial drill holes. The anterior longitudinal limb then undergoes controlled fracture by placement of 2 to 4 broad straight osteotomes in the posterior longitudinal limb. These osteotomes are carefully levered anteriorly in unison with a gentle, steady force. After the ETO is completed, intramedullary prostheses, hardware, and cement are removed; the acetabulum is addressed as needed; and a final femoral stem is implanted, if appropriate. After completion of the osteotomy, the osteotomized fragment must be retracted gently, with care taken to avoid a fracture and maintain vascularity. To this end, debridement of the endosteum of the osteotomized fragment, including any cement removal, should be avoided until the end of the procedure, when the osteotomy is ready to be closed. Our preferred method for closure is to place 1 prophylactic cable 1 cm distal to the osteotomy, 1 to 2 cables along the diaphyseal segment of the osteotomy, and 1 Luque wire above the less trochanter. A Luque wire is our specific choice for the location above the lesser trochanter because it sits in the effective joint space; however, the use of Luque wires distal to the lesser trochanter is also acceptable. A strut allograft or locking plate can be utilized to reinforce the osteotomy in rare cases or to bridge interprosthetic stress risers. Trochanteric implants are typically avoided because of the low rate of clinically relevant trochanteric migration with this closure technique and because of the high rate of symptomatic implants with trochanteric claws or plates. Alternatives: An alternative osteotomy of similar exposure is the transfemoral osteotomy. Additionally, a variety of non-extended trochanteric osteotomies, such as trochanteric slide osteotomies, offer more limited exposure. Rationale: Femoral surgical exposure for revision THA can be aided by performing transfemoral osteotomies, but these provide less precise control of the separate proximal femoral osteotomized segment(s), and healing and fixation can be less reliable. Less invasive osteotomies such as non-extended trochanteric osteotomies typically do not provide adequate exposure in challenging cases for which ETO is being considered. Expected Outcomes: ETOs have high union rates, and notable trochanteric migration is infrequent. The most common complications are fracture of the osteotomy fragment intraoperatively or postoperatively. Radiographic and clinical union is achieved in 98% of patients. The mean proximal trochanteric osteotomy fragment migration prior to union is 3 mm. ETO fragment migration of >1 cm occurs in just 7% of hips. Postoperative greater trochanter fractures occur in 9% of hips. The 10-year survivorship free of revision for aseptic femoral loosening, free of femoral or acetabular component removal or revision for any reason, and free of reoperation for any reason is 97%, 91%, and 82%, respectively 3 . Important Tips: Attention should be paid to patient anatomy, deformity, surgical approach, and implant type when choosing to perform a laterally based Paprosky or anteriorly based Wagner ETO. Appropriate length of the posterior longitudinal limb of the ETO is approximately 12 to 16 cm distally from the tip of the greater trochanter. Attention must be paid to maintaining vascularity to the osteotomy fragment, including minimizing stripping of the vastus lateralis from the osteotomy fragment and maintaining abductor attachments to the osteotomy fragment. A high-speed pencil-tip burr should be utilized to complete the corners of the osteotomy in a rounded configuration in order to avoid stress risers. The anterior longitudinal limb is completed by controlled fracture of the remaining intervening segment in order to maintain vastus lateralis attachments and vascular supply to the osteotomy fragment. The ETO is closed with use of cerclage cables and/or double-stranded Luque wires, typically utilizing a total of 3 to 4 in order to obtain secure fixation without compromising local biology. Acronyms and Abbreviations: MFT = modular fluted tapered

AbstractHuman lifespan continues to extend as an unprecedented number of people reach their seventh and eighth decades of life, unveiling chronic conditions that affect the older adult. Age-related skin conditions include senile purpura, seborrheic keratoses, pemphigus vulgaris, bullous pemphigoid, diabetic foot wounds and skin cancer. Current methods of drug testing prior to clinical trials require the use of pre-clinical animal models, which are often unable to adequately replicate human skin response. Therefore, a reliable model for aged human skin is needed. The current challenges in developing an aged human skin model include the intrinsic variability in skin architecture from person to person. An ideal skin model would incorporate innate functionality such as sensation, vascularization and regeneration. The advent of 3D bioprinting allows us to create human skin equivalent for use as clinical-grade surgical graft, for drug testing and other needs. In this review, we describe the process of human skin aging and outline the steps to create an aged skin model with 3D bioprinting using skin cells (i.e. keratinocytes, fibroblasts and melanocytes). We also provide an overview of current bioprinted skin models, associated limitations and direction for future research.

Summary: Aging of the face is the result of the interrelation of three-dimensional changes occurring over time among the 5 different layers of the face and its associated structures. Knowledge regarding the causes of these changes and identification of new key anatomic structures have helped elucidate one of the most complex areas of the human body. This has resulted in the introduction of pharmacologic agents to help stop, mitigate, or counteract signs of aging and restore the youthful appearance of the face. The authors performed a systematic search of the literature to review the current highest-level evidence of facial antiaging pharmacologic agents. Pharmacologic and minimally invasive antiaging treatments can target different components of facial aging and continue to evolve. With continuous research efforts, traditional treatments, such as botulinum toxin type A, injectable fillers, and chemical peels, are emerging in newer, more effective formulations, with longer lasting clinical results. However, for soft-tissue descent and facial volume loss, surgery remains the standard treatment. An adequate understanding of the three-dimensional process of facial aging over time (the fourth dimension), facial anatomy, and the pharmacologic properties of antiaging/rejuvenation agents are the sine qua non of facial antiaging treatment. The specific modality should be tailored to patient characteristics, preferences, and goals.