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Leber congenital amaurosis due to CEP290 ciliopathy is being explored by treatment with an antisense oligonucleotide (AON) sepofarsen. One individual who was part of a larger cohort (ClinicalTrials.gov no. NCT03140969) was studied for 15 months after a single intravitreal sepofarsen injection. Concordant measures of visual function and retinal structure reached a substantial efficacy peak near 3 months post-injection. At 15 months, there was sustained efficacy even though there was evidence of reduction from peak response. Efficacy kinetics can be explained by the balance of AON-driven new CEP290 protein synthesis and a slow natural rate of CEP290 protein degradation in human foveal cone photoreceptors.

Health-related quality of life is a comprehensive term to describe a person's experiences of health and illness. Quality of life (QOL) is a dynamic psychological construct encompassing interacting subjective and objective dimensions; thus, it is not directly observable. There is no gold standard for measuring quality of life due to the differing interests of doctors, caregivers, patients, and researchers. This chapter examines the research needs in the area of improving QoL through the proper implementation of AT. The authors also make recommendations for incorporating the needs of users and caregivers in the design, deployment, and use of AT to reduce device abandonment.

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 (NCT03140969), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit–risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.

Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. There were no serious adverse events, and vision improved at 3 months. The visual acuity of one exceptional responder improved from light perception to 20/400. RNA antisense oligonucleotide therapy to restore normal splicing of a ciliopathy gene shows promising safety and efficacy results in a clinical trial to treat a form of childhood blindness.

Congenital chest wall abnormalities are an array of malformations that are caused by inappropriate embryological formation of the rib cage. These abnormalities are often associated with other skeletal dysplasias. Chest wall anomalies may also be associated with syndromes that may affect other organ systems. The spectrum of deformities range from common, mostly benign malformations, such as pectus excavatum, to very rare and usually fatal abnormalities, such as ectopia cordis with associated Pentalogy of Cantrell. The anesthesia team should be aware of these deformities and issues that may arise while managing patients who present with them. This chapter will discuss several congenital chest wall abnormalities and the current anesthetic management of these interesting and challenging malformations.

The Nuss procedure was introduced in 1998 as a less invasive surgical technique for correction of the chest wall deformity, pectus excavatum (PE). This chapter summarizes the clinical picture of PE, describes the Nuss procedure and explores the anesthetic requirements for a patient undergoing the procedure. The criteria for surgical correction and preoperative planning is outlined. Known and potential complications are discussed. Intra and postoperative pain management often presents a challenge to the anesthesiologist, therefore different methods of analgesia are examined. Multiple reviews of surgical outcomes describe success of the procedure as the surgical technique has been refined through the years.

Breast asymmetry has been described as early as 1841 when Poland described the eponymous syndrome of chest wall deformity that can include musculoskeletal, breast and nipple malformations. While most patients have some asymmetry of the breast, there can be significant differences in size, shape and position in some patients requiring unique thought and approach to achieve satisfying aesthetic and symmetry goals for the patient and surgeon. Breast symmetry can have a significant psychological effects.

Background: Sepofarsen is an RNA antisense oligonucleotide (AON) targeting the common c.2991+1655A>G mutation in the CEP290 gene to treat Leber congenital amaurosis type 10 (LCA10), a condition with severe childhood-onset vision loss or blindness. Methods: In this 12-month, multicenter, open-label, multiple-dose, dose-escalation, phase 1b/2 trial, patients with LCA10 received up to four doses of intravitreal sepofarsen in the worse-seeing eye. Primary end point was safety; secondary end points included vision outcome measures. Findings: Of 11 patients enrolled (8–44 years of age), six received loading/maintenance doses of sepofarsen of 160 µg/80 µg and five received 320 µg/160 µg. Reported cases of cataracts, mild cystoid macular edema, and retinal thinning were 3, 0, and 0, respectively, in the 160-µg/80-µg group and 5, 2, and 2 in the 320-µg/160-µg group. Pooled data (n=11) showed improvements from baseline to Month 12 in treated eyes vs untreated eyes in mean ± standard error of the mean best-corrected visual acuity (BCVA: −0·55 ± 0·26 vs −0·12 ± 0·07 logarithm of the minimum angle of resolution [logMAR], p

In 1985 this cleft team, dissatisfied with the treatment and results from cleft lip and palate repair, began a longitudinal long-term study using dynamic maxillary orthopedics and periosteoplasty as was originally described by Drs Millard and Latham. All cases were carefully documented through adolescence, including clinical assessments, orthodontic, radiographic, and cephalometric analyses. In 1998, in this journal, we published our data on 35 complete unilateral and 10 complete bilateral cleft patients. At that time facial growth was following normal cephalometric patterns. Crossbites were dental and treated with orthodontics. There was radiologic evidence of bone within the alveolus with elimination of the oronasal fistula, and facial aesthetics revealed soft faded scars and balanced noses.That publication was a preliminary study with the intent to provide long-term results when full facial growth was achieved. This article reports on 25 patients from the initial cohort (20 unilateral and 5 bilateral) that we were able to closely follow up for 25 years, with the same clinical team, making it the longest study of its kind.At this stage, data revealed continued growth of the midface both vertically and horizontally. Secondary alveolar cleft bone grafting when required was in small aliquots placed into well-healed tissue, and orthodontic movement of teeth was through a consolidated alveolus. Orthognathic procedures were performed in 2 of 5 bilateral and 0 of 20 unilateral cases.We concluded that in this cohort, dynamic maxillary orthopedics and periosteoplasty, despite controversy in the literature, did not negatively impact facial growth and provided the benefit of early structural normalization and social integration by consolidation of the maxilla, closure of the oronasal fistula, tension free closure of the lip, and by balancing the nose.

Background Board-certified plastic surgeons utilizing the Sientra 207 Highly Cohesive Gel breast implants provided their initial satisfaction with usage and postoperative results on primary and revision augmentation patients, and study participants provided their satisfaction with surgical result. Methods Up to 15 participating investigators at institutional review board-approved sites enrolled up to 180 women who received Sientra 207 implants for primary augmentation or revision augmentation procedures. Investigator and participant assessments were performed preoperatively and postoperatively at 3, 6, and 12 months. Results All participating surgeons found the implants to be easy or very easy to implant, and 92 percentage reported satisfaction with surgical results. Patients receiving these implants reported similarly high rates of satisfaction (94%). Conclusion With this combination of high satisfaction and low complication rates, the Sientra 207 silicone breast implants now provide a welcome addition to plastic surgeons' breast implant options.

The ability to procure and allocate organs is dependent on patient comorbidities, logistical factors and ethical considerations. The anesthesia team plays a critical role in supporting organ donation which may include donation after brain death (DBD) or donation after cardiac death (DCD) procurements. Careful monitoring and management of the donor patient’s circulatory, respiratory, hematologic and endocrine parameters specific to organ donation type can improve transplant outcomes for the recipient.

In this review, the authors provide a 20-year review and comparison of implant options and describe the evolution of breast implant surface textures; compare available implant surfaces; present long-term safety data from the 10-year US-based Core clinical studies; list the key benefits and risks associated with smooth and textured implants; and provide perspectives on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The authors explore the key benefits and risks associated with all available devices so that optimal and safe patient outcomes can be achieved.

After reading this article, the participant should be able to: 1. Understand the key decisions in patient evaluation for cosmetic breast augmentation. 2. Cite key decisions in preoperative planning. 3. Discuss the risks and complications, and key patient education points in breast augmentation.Breast augmentation remains one of the most popular procedures in plastic surgery. The integral information necessary for proper patient selection, preoperative assessment, and surgical approaches are discussed. Current data regarding long term safety and complications are presented to guide the plastic surgeon to an evidence-based approach to the patient seeking breast enhancement to obtain optimal results.

With the 2006 Food and Drug Administration approval of round silicone gel breast implants in the United States, there still remained a lack of versatility in implant options. The approval of Sientra's shaped cohesive implants in 2012 brought with it the innovations needed to address varying patient needs. Because access to shaped devices is still fairly recent in the United States, some surgeons remain uncomfortable with implementing shaped cohesive gel implants into their practice. The author outlines surgical techniques and algorithms from experience with the Sientra shaped device, covering the preoperative stage, measurements (base diameter, sternal notch to nipple, tissue pinch, and nipple to inframammary fold), ideal first candidates, operative techniques, and complication avoidance, as well as important factors for shaped-implant selection, including chest base diameter, implant height, implant volume, and implant projection for the patient's desired outcome. With experience, surgeons will find new utility with shaped implants for a variety of patients in their practices.

A panel of board-certified plastic surgeons chaired by Dr Michael Schwartz convened to discuss their respective experiences with the Sientra High-Strength Cohesive (HSC+) shaped silicone gel breast implants (Sientra, Inc., Santa Barbara, CA). The authors have implanted a combined total of over 700 patients. Preoperative planning, surgical techniques, and practice integration tips are among the topics reviewed. The surgeons also present breakthrough cases and describe how the HSC+ textured implants helped them achieve a successful outcome. Level of Evidence 5![Graphic][1] Therapeutic [1]: /embed/inline-graphic-1.gif

The Sientra portfolio of silicone gel breast implants was approved by the Food and Drug Administration on March 9, 2012, and included the first approved shaped implants in the United States. The 5-year results from Sientra's Core Gel and Continued Access Study and the results of a single surgeon are presented.This analysis used the data of 640 shaped implants in 321 primary augmentation patients implanted by 16 study surgeons through 5 years. The Kaplan-Meier method was used to analyze safety endpoints. In addition, analysis is presented for a single surgeon's results of 213 shaped implants in 108 postapproval patients through up to 16 months of follow-up (9-month mean) using a separate frequency analysis.The overall risk of rupture for primary augmentation patients through 5 years was 0.4%, the risk of infection was 1.4%, and the risk of capsular contracture (Baker grade III/IV) was 3.9%. Reported surgeon satisfaction was 100%, and patient satisfaction remained high. In the separate single-surgeon analysis, after 16 months, 4 of the 108 patients experienced a complication (3.7%) and 3 underwent a reoperation (2.8%). Complications included infection, ptosis (0.9%, each), and capsular contracture (1.9%).The results of Sientra's large clinical study and the postapproval data from a single surgeon demonstrate the safety and effectiveness of Sientra's shaped implants. The review of the data and author's experience illustrate the ease of incorporating shaped implants into any surgical practice.

In 1990, Drs Millard and Latham published their initial experience with dynamic maxillary appliances (DMAs) and periosteoplasty for children with cleft lip and palate. The technique provided for alveolar alignment and consolidation, with elimination of oronasal fistulas. Opponents to this approach speculated about impairments to facial growth. To date no longitudinal studies have been published. Over the last 10 years, 35 unilateral and 10 bilateral complete clefts have been treated with this technique. All patients have been followed and documented clinically, orthodontically, and radiographically. Cephalometric analyses were performed on children after the age of 6 years. The children have excellent facial aesthetics with well-balanced lips and noses. Radiographs demonstrate bone within the repaired alveolar clefts. Articulated impressions show anterior and lateral crossbites in the unilateral patients that improve over time and appear to be correctable orthodontically. The bilateral patients have satisfactory occlusions and arch forms. Cephalometric analyses confirmed no evidence of skeletal crossbites or midfacial growth retardation. This is a work in progress that will continue as the children grow. Although definite and final conclusions would be premature, it can be stated that to date all patients are following consistent and favorable growth patterns. Our team is confident in proceeding with this technique.

Purpose: Five hundred fourteen consecutive patients with an isolated upper or lower extremity penetrating injury were entered into a prospective study designed to refine the indications for diagnostic arteriography. Methods: Twenty-two (4%) patients with limb-threatening ischemia who required immediate operation and 23 (4%) who refused arteriography were excluded from subsequent analyses. The remaining 469 patients were classified as being at high, intermediate, or low risk for an arterial injury. Results: Two hundred thirteen patients who were at low risk were observed for 24 hours, discharged, and monitored as outpatients. No delayed complications of an arterial injury developed in any patient in this group. The intermediate-risk group of 151 patients and the high-risk group of 105 patients underwent arteriography. Seventy-seven injuries were identified; 24 were major (limb-threatening) and 53 were minor. Fourteen major injuries required operative repair or transcatheter embolization; the remaining 10 nonocclusive major injuries were observed without sequelae. Conclusions: By step-down logistic regression only pulse deficit (p ASC S URG 1993;17:116-24.)

The nasal dermal sinus cyst is one of many midline nasal masses that often pose diagnostic and treatment dilemmas for the plastic and reconstructive surgeon. The differential diagnosis of the midline nasal mass includes both congenital and acquired processes. A thorough understanding of its cause is crucial to treatment. A comprehensive discussion of the pathogenesis, diagnosis, sequelae, and surgical management, and a representative case analysis, of the nasal dermal sinus cyst is presented to delineate the role of open rhinoplasty in optimizing the care of this congenital nasal deformity.