Hazard of Failed Nonoperative Management for Symptomatic Accessory Navicular in Children and Adolescents: A Population-Based Case-Cohort Study.

BACKGROUND: The accessory navicular (AN) is an idiopathic condition of the foot present in 4% to 21% of the population. Most ANs remain asymptomatic, but children and adolescents who develop symptoms can have remarkably reduced quality of life. Although many respond to conservative measures, surgery is occasionally needed. Our purpose was to determine factors associated with the failure of nonoperative management. METHODS: This single-institution retrospective case-cohort study included patients up to age 19 years presenting between 2000 and 2021 with symptomatic AN and treated with standard-of-care. All 298 surgical cases, indicating failed nonoperative treatment, were included. For the subcohort, 299 patients were randomly sampled from all eligible patients, regardless of treatment. Baseline characteristics were summarized for the surgical cases and subcohort. Proportional hazards assumptions were checked and stratification implemented when necessary. Marginal structural proportional hazard modeling was used to estimate hazard ratios with 95% confidence intervals via inverse probability and LinYing weighting methods. RESULTS: The 298 surgical cases failed nonoperative management at a median of 5.2 months (IQR, 2.0-11.6 mo). In the subcohort, 86 failures of nonoperative management and 213 nonfailures constituted a 28.8% surgery rate. In both cohorts, nearly all patients played sports. Univariate proportional hazard modeling found older age (P=0.02) and activity limitation (P<0.001) at presentation, female sex (P=0.002), higher BMI (P=0.01), AN on the right (P<0.001), and bone marrow edema of the AN (P<0.001) and navicular body (P<0.001) on MRI were associated with increased hazard of nonoperative failure. Nearly all of the surgical cohort reported improvement in pain (278/296, 94%) and returned to their primary sport (236/253, 93%) after surgery. Most also experienced full resolution of symptoms (187/281, 67%). CONCLUSIONS: Symptomatic AN predominantly affects female athletes, leading to surgery in 28.8% of our subcohort. Conservative treatment may be less successful-and therefore surgery could be more strongly considered-in older age, activity limitation at presentation, female sex, higher BMI, right-sided AN, and bone marrow edema on MRI. Surgery is effective for symptomatic and functional improvement. LEVEL OF EVIDENCE: Case-cohort-Level III.

Strain of Multidrug-Resistant Salmonella Newport Remains Linked to Travel to Mexico and U.S. Beef Products - United States, 2021-2022.

In 2016, CDC identified a multidrug-resistant (MDR) strain of Salmonella enterica serotype Newport that is now monitored as a persisting strain (REPJJP01). Isolates have been obtained from U.S. residents in all 50 states and the District of Columbia, linked to travel to Mexico, consumption of beef products obtained in the United States, or cheese obtained in Mexico. In 2021, the number of isolates of this strain approximately doubled compared with the 2018-2020 baseline and remained high in 2022. During January 1, 2021- December 31, 2022, a total of 1,308 isolates were obtained from patients, cattle, and sheep; 86% were MDR, most with decreased susceptibility to azithromycin. Approximately one half of patients were Hispanic or Latino; nearly one half reported travel to Mexico during the month preceding illness, and one third were hospitalized. Two multistate outbreak investigations implicated beef products obtained in the United States. This highly resistant strain might spread through travelers, animals, imported foods, domestic foods, or other sources. Isolates from domestic and imported cattle slaughtered in the United States suggests a possible source of contamination. Safe food and drink consumption practices while traveling and interventions across the food production chain to ensure beef safety are necessary in preventing illness.

Polyomavirus Wakes Up and Chooses Neurovirulence.

JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has "reemerged" as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease.

Lysophosphatidic acid signaling via LPA6 : A negative modulator of developmental oligodendrocyte maturation.

The developmental process of central nervous system (CNS) myelin sheath formation is characterized by well-coordinated cellular activities ultimately ensuring rapid and synchronized neural communication. During this process, myelinating CNS cells, namely oligodendrocytes (OLGs), undergo distinct steps of differentiation, whereby the progression of earlier maturation stages of OLGs represents a critical step toward the timely establishment of myelinated axonal circuits. Given the complexity of functional integration, it is not surprising that OLG maturation is controlled by a yet fully to be defined set of both negative and positive modulators. In this context, we provide here first evidence for a role of lysophosphatidic acid (LPA) signaling via the G protein-coupled receptor LPA6 as a negative modulatory regulator of myelination-associated gene expression in OLGs. More specifically, the cell surface accessibility of LPA6 was found to be restricted to the earlier maturation stages of differentiating OLGs, and OLG maturation was found to occur precociously in Lpar6 knockout mice. To further substantiate these findings, a novel small molecule ligand with selectivity for preferentially LPA6 and LPA6 agonist characteristics was functionally characterized in vitro in primary cultures of rat OLGs and in vivo in the developing zebrafish. Utilizing this approach, a negative modulatory role of LPA6 signaling in OLG maturation could be corroborated. During development, such a functional role of LPA6 signaling likely serves to ensure timely coordination of circuit formation and myelination. Under pathological conditions as seen in the major human demyelinating disease multiple sclerosis (MS), however, persistent LPA6 expression and signaling in OLGs can be seen as an inhibitor of myelin repair. Thus, it is of interest that LPA6 protein levels appear elevated in MS brain samples, thereby suggesting that LPA6 signaling may represent a potential new druggable pathway suitable to promote myelin repair in MS.

UV-based advanced oxidation of dissolved organic matter in reverse osmosis concentrate from a potable water reuse facility: A Parallel-Factor (PARAFAC) analysis approach.

Disposal of reverse osmosis concentrate (ROC) from advanced water purification facilities is a challenge associated with the implementation of reverse osmosis-based treatment of municipal wastewater effluent for potable reuse. In particular, the dissolved organic matter (DOM) present in ROC diminishes the quality of the receiving water upon environmental disposal and affects the toxicity, fate, and transport of organic contaminants. This study investigates UV-based advanced oxidation processes (UV-AOPs) for treating DOM in ROC using a Parallel Factor Analysis (PARAFAC) approach. DOM composition and degradation were tested in UV-only and three UV-AOPs using hydrogen peroxide (H2O2), free chlorine (Cl2), and persulfate (S2O82-). The four-component PARAFAC model consisted of two terrestrial humic-like components (CUVH and CVisH), a wastewater/nutrient tracer component (CNuTr), and a protein-like (tyrosine-like) component (CPrTy). Based on the observed loss in the maximum fluorescence intensity of the components, DOM degradation was determined to be dependent on UV fluence, oxidant dose, and dilution factor of the ROC (i.e., bulk DOM concentration). CVisH was most the photolabile component in the UV-only system, followed by CNuTr, CPrTy, and CUVH, respectively. Furthermore, UV-H2O2 and UV-S2O82- displayed faster overall reaction kinetics compared to UV-Cl2. The degradation trends suggested that CNuTr and CPrTy consisted of chemical moieties that were susceptible to reactive oxygen species (HO•) but not reactive chlorine species; whereas, CVisH was sensitive to all reactive species generated in the three UV-AOPs. Compared to other components, CPrTy was recalcitrant in all treatment scenarios tested. Calculations using chemical probe-based analysis also confirmed these trends in the reactivity of DOM components. The outcomes of this study form a foundation for characterizing ROC reactivity in UV-AOP treatment technologies, to ultimately improve the sustainability of water reuse systems.

Epiphysiodesis for Leg Length Discrepancy: A Cost Analysis of Drill Versus Screw Technique.

Research has demonstrated similar efficacy of drill epiphysiodesis and percutaneous epiphysiodesis using transphyseal screws for the management of adolescent leg length discrepancy. A cost analysis was performed to determine which procedure is more cost-effective. Patients seen for epiphysiodesis of the distal femur and/or proximal tibia and fibula between 2004 and 2017 were reviewed. A decision analysis model was used to compare costs. Two hundred thirty-five patients who underwent either drill (155/235, 66%) or screw (80/235, 34%) epiphysiodesis were analyzed with an average age at initial procedure of 13 years (range, 8.4 to 16.7 years). There was no significant difference in average initial procedure cost or total cost of all procedures across treatment groups (n = 184). The cost difference between drill and screw epiphysiodesis is minimal. In order for screw epiphysiodesis to be cost-favored, there would need to be a significant decrease in its cost or complication rate. (Journal of Surgical Orthopaedic Advances 30(3):181-184, 2021).

Prospective Evaluation of Tarsal Coalition Excision Show Significant Improvements in Pain and Function.

BACKGROUND: Excision of pediatric tarsal coalition has been successful in most patients. However, some patients have ongoing pain after coalition excision. This study prospectively assessed patient-based clinical outcomes before and after surgical excision of tarsal coalition, with particular emphasis on comparison to radiologic imaging. METHODS: We prospectively studied 55 patients who had symptomatic coalition excision for 2 years postoperatively. Patients filled out the modified American Orthopaedic Foot and Ankle Society score, the University of California Los Angeles activity score, and the simple question "does foot pain limit your activity" at 4 different time points: preoperative, 6 months postoperative, 12 months postoperative, and 24 months postoperative. Comparisons were done utilizing patient demographics, imaging parameters, and patient-reported outcomes. RESULTS: Compared with preoperative levels, patients showed improvements in all outcome parameters. Patients with calcaneonavicular coalitions showed initial rapid improvement with later slight decline, while patients with talocalcaneal coalitions showed more steady improvement; both were similar at 2 years postoperatively. CONCLUSIONS: This prospective study demonstrated remarkable clinical improvements after tarsal coalition excision regardless coalition type, though postoperative courses differed between calcaneonavicular and talocalcaneal types. Finally, a subset of patients has ongoing activity limiting foot pain after coalition excision which could not be explained by the data in this study. LEVEL OF EVIDENCE: Level II-prospective cohort study.

Surgical Treatment of Solitary Periarticular Osteochondromas About the Knee in Pediatric and Adolescent Patients: Complications and Functional Outcomes.

BACKGROUND: Solitary osteochondromas, or osteocartilaginous exostoses (OCEs), represent the most common benign bone tumor. Despite frequently causing symptoms about the knee in younger populations, there is minimal previous literature investigating surgical treatment. METHODS: We retrospectively reviewed the records of patients <20 years old who had undergone surgical treatment of symptomatic, pathologically confirmed, solitary periarticular knee OCE at a single pediatric center between 2003 and 2016. The clinical course, radiographic and pathological features, and complications were assessed. Prospective outreach was performed to investigate patient-reported functional outcomes. RESULTS: Two hundred and sixty-four patients (58% male, 81% athletes) underwent excision of a solitary OCE about the knee at a mean age (and standard deviation) of 14.3 ± 2.24 years. Fifty-five percent of the procedures were performed by orthopaedic oncologists, 25% were performed by pediatric orthopaedic surgeons, and 20% were performed by pediatric orthopaedic sports medicine surgeons, with no difference in outcomes or complications based on training. Of the 264 lesions, 171 (65%) were pedunculated (versus sessile), 157 (59%) were in the distal part of the femur (versus the proximal part of the tibia or proximal part of the fibula), and 182 (69%) were medial (versus lateral). Postoperatively, 96% of the patients returned to sports at a median of 2.5 months (interquartile range, 1.9 to 4.0 months). Forty-two patients (16%) experienced minor complications not requiring operative intervention. Six patients (2%) experienced major complications (symptoms or disability at >6 months or requiring reoperation), which were more common in patients with sessile osteochondromas (p = 0.01), younger age (p = 0.01), and distal femoral lesions as compared with proximal tibial lesions (p = 0.003). Lesion recurrence was identified in 3 patients (1.1%). Overall, the median Pediatric International Knee Documentation Committee (Pedi-IKDC) and mean Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) scores were 97 (interquartile range, 93 to 99) and 16.7 ± 8.15, respectively, at a median duration of follow-up of 5.8 years. CONCLUSIONS: In our large cohort of pediatric patients who underwent excision of solitary knee osteochondromas, most patients were male adolescent athletes. Most commonly, the lesions were pedunculated, were located in the distal part of the femur, and arose from the medial aspect of the knee. Regardless of surgeon training or lesion location, patients demonstrated excellent functional outcomes, with minimal clinically important postoperative complications and recurrences, although patients with sessile lesions and younger age may be at higher risk for complications. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Best practice guidelines in managing the craniofacial aspects of skeletal dysplasia.

BACKGROUND: Recognition and appropriate management of the craniofacial manifestations of patients with skeletal dysplasia are challenging, due to the rarity of these conditions, and dearth of literature to support evidence-based clinical decision making. METHODS: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, best practice guidelines in the management of craniofacial aspects of these patients. RESULTS: After a comprehensive literature review, 23 initial statements were generated and critically discussed, with subsequent development of a list of 22 best practice guidelines after a second round voting. CONCLUSIONS: The guidelines are presented and discussed to provide context and assistance for clinicians in their decision making in this important and challenging component of care for patients with skeletal dysplasia, in order standardize care and improve outcomes.

Classification of lower extremity venous malformations and risk of knee involvement: A retrospective cohort study.

BACKGROUND: Venous malformation (VM) is the most common vascular anomaly in the lower extremity. VMs can be classified as focal, multifocal, or diffuse types. Intraarticular VM (IA-VM) of the knee portends morbidity. Association of the lower extremity VM type with IA-VM is not well defined. OBJECTIVE: To classify a large cohort of lower extremity, nonsyndromic VMs by type and determine associations with IA-VM. METHODS: Retrospective cohort study. RESULTS: We assessed 156 patients with nonsyndromic, lower extremity VM; 71 (46%) were focal and 85 (54%) were diffuse type VM, and 97 (62%) were IA-VM. Of diffuse VMs, 26 (31%) were Bockenheimer and 59 (69%) were localized subtypes. Pure VM had a significantly elevated risk of IA-VM (relative risk [RR], 2.34; 95% confidence interval [CI], 1.42-3.89). IA-VM was more common in diffuse (73%) versus focal (49%) types. Risk of IA-VM in diffuse type VM was significantly elevated (RR, 1.48; 95% CI, 1.13-1.94). One hundred percent of diffuse Bockenheimer type VM had IA-VM, and this subtype had the highest risk (RR, 1.83; 95% CI, 1.56-2.14) of IA-VM. LIMITATIONS: Retrospective, single-institution study. CONCLUSIONS: Intraarticular involvement of the knee should be considered in all lower extremity VMs. Pure VM and the Bockenheimer diffuse VM subtype had the highest risk of IA-VM.

College of American Pathologists Cancer Protocols: From Optimizing Cancer Patient Care to Facilitating Interoperable Reporting and Downstream Data Use.

The College of American Pathologists Cancer Protocols have offered guidance to pathologists for standard cancer pathology reporting for more than 35 years. The adoption of computer readable versions of these protocols by electronic health record and laboratory information system (LIS) vendors has provided a mechanism for pathologists to report within their LIS workflow, in addition to enabling standardized structured data capture and reporting to downstream consumers of these data such as the cancer surveillance community. This paper reviews the history of the Cancer Protocols and electronic Cancer Checklists, outlines the current use of these critically important cancer case reporting tools, and examines future directions, including plans to help improve the integration of the Cancer Protocols into clinical, public health, research, and other workflows.

The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor.

Understanding how fate specification of distinct cell-types from multipotent progenitors occurs is a fundamental question in embryology. Neural crest stem cells (NCSCs) generate extraordinarily diverse derivatives, including multiple neural, skeletogenic and pigment cell fates. Key transcription factors and extracellular signals specifying NCSC lineages remain to be identified, and we have only a little idea of how and when they function together to control fate. Zebrafish have three neural crest-derived pigment cell types, black melanocytes, light-reflecting iridophores and yellow xanthophores, which offer a powerful model for studying the molecular and cellular mechanisms of fate segregation. Mitfa has been identified as the master regulator of melanocyte fate. Here, we show that an Mitf-related transcription factor, Tfec, functions as master regulator of the iridophore fate. Surprisingly, our phenotypic analysis of tfec mutants demonstrates that Tfec also functions in the initial specification of all three pigment cell-types, although the melanocyte and xanthophore lineages recover later. We show that Mitfa represses tfec expression, revealing a likely mechanism contributing to the decision between melanocyte and iridophore fate. Our data are consistent with the long-standing proposal of a tripotent progenitor restricted to pigment cell fates. Moreover, we investigate activation, maintenance and function of tfec in multipotent NCSCs, demonstrating for the first time its role in the gene regulatory network forming and maintaining early neural crest cells. In summary, we build on our previous work to characterise the gene regulatory network governing iridophore development, establishing Tfec as the master regulator driving iridophore specification from multipotent progenitors, while shedding light on possible cellular mechanisms of progressive fate restriction.

Orthopedic issues in vascular anomalies.

Vascular anomalies impact the musculoskeletal system dependent on the tissue involved (skin, subcutis, muscle, cartilage, or bone), the extent of involvement, and the type of anomalous vessels (arteries, capillaries, veins, or lymphatics). These malformations can cause a multitude of musculoskeletal problems for the patient. Leg-length discrepancy, intra-articular involvement, muscular lesions, and primary or secondary scoliosis are amongst the issues that patients face. All of these problems can cause pain, deformity, and a range of functional limitations. Surgical and nonsurgical treatment plans have a role in patient care. Patients with vascular anomalies may also suffer from life-threatening cardiovascular and hematologic abnormalities. For those patients who undergo surgery, the thromboembolic risk is elevated, wound breakdown and infection are much more common, and bleeding risk continues well into the postoperative course. Because of the complex nature of these disorders, the clinician must have a full understanding of the types of lesions, their natural history, appropriate diagnostic studies, associated medical problems, indications for treatment, and treatment options. For severe malformations, especially syndromes such as CLOVES and Klippel- Trenaunay syndrome, interdisciplinary team management is essential for the best outcomes.

Best practice guidelines for management of spinal disorders in skeletal dysplasia.

BACKGROUND: Disorders of the spine present a common and difficult management concern in patients with skeletal dysplasia. Due to the rarity of these conditions however, the literature, largely consisting of small, single institution case series, is sparse in regard to well-designed studies to support clinical decision making in these situations. METHODS: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, "best practice" guidelines in the care of spinal disorders in patients with skeletal dysplasia. RESULTS: Starting with 33 statements, the group a developed a list of 31 "best practice" guidelines. CONCLUSIONS: The guidelines are presented and discussed to provide context for clinicians in their decision making in this often-challenging realm of care.

Mitf-family transcription factor function is required within cranial neural crest cells to promote choroid fissure closure.

A crucial step in eye development is the closure of the choroid fissure (CF), a transient structure in the ventral optic cup through which vasculature enters the eye and ganglion cell axons exit. Although many factors have been identified that function during CF closure, the molecular and cellular mechanisms mediating this process remain poorly understood. Failure of CF closure results in colobomas. Recently, MITF was shown to be mutated in a subset of individuals with colobomas, but how MITF functions during CF closure is unknown. To address this issue, zebrafish with mutations in mitfa and tfec, two members of the Mitf family of transcription factors, were analyzed and their functions during CF closure determined. mitfa;tfec mutants possess severe colobomas and our data demonstrate that Mitf activity is required within cranial neural crest cells (cNCCs) during CF closure. In the absence of Mitf function, cNCC migration and localization in the optic cup are perturbed. These data shed light on the cellular mechanisms underlying colobomas in individuals with MITF mutations and identify a novel role for Mitf function in cNCCs during CF closure.

Enteral tube administration of oral chemotherapy drugs.

Objective: Patients receiving oral chemotherapies face treatment interruptions if they require placement of an enteral tube for nutrition, potentially leading to adverse outcomes in cancer treatment. Enteral tube medication administration can provide a suitable alternative. The purpose of this review is to compile available data that describe enteral tube administration of oral chemotherapy agents. Data sources: A systematic evaluation of all Food and Drug Administration-approved oral chemotherapy agents through 31 July 2019 was conducted. Information on crushing or opening of the tablet or capsule, enteral tube administration, and extemporaneous formulations was compiled from the prescribing information, tertiary resources, and primary literature. Drug manufacturers were contacted for additional information. Data summary: A total of 87 oral chemotherapy agents were evaluated. Of the 87 drugs, 33 agents (37.9%) had information regarding enteral tube administration with only four drugs with nasogastric or gastric tube administration instructions in their prescribing information. The strength of evidence varied from non-peer reviewed data to complete evaluations of efficacy and safety. The majority of chemotherapies (62%) had no available data on enteral tube administration. Conclusions: The results of this review suggest that there is limited data surrounding enteral tube administration of most oral chemotherapies, demonstrating the need for more studies to be conducted to provide more guidance to healthcare providers when administration via an enteral tube is needed in their patients.

Sodium-Calcium Exchangers of the SLC8 Family in Oligodendrocytes: Functional Properties in Health and Disease.

The solute carrier 8 (SLC8) family of sodium-calcium exchangers (NCXs) functions as an essential regulatory system that couples opposite fluxes of sodium and calcium ions across plasmalemmal membranes. NCXs, thereby, play key roles in maintaining an ion homeostasis that preserves cellular integrity. Hence, alterations in NCX expression and regulation have been found to lead to ionic imbalances that are often associated with intracellular calcium overload and cell death. On the other hand, intracellular calcium has been identified as a key driver for a multitude of downstream signaling events that are crucial for proper functioning of biological systems, thus highlighting the need for a tightly controlled balance. In the CNS, NCXs have been primarily characterized in the context of synaptic transmission and ischemic brain damage. However, a much broader picture is emerging. NCXs are expressed by virtually all cells of the CNS including oligodendrocytes (OLGs), the cells that generate the myelin sheath. With a growing appreciation of dynamic calcium signals in OLGs, NCXs are becoming increasingly recognized for their crucial roles in shaping OLG function under both physiological and pathophysiological conditions. In order to provide a current update, this review focuses on the importance of NCXs in cells of the OLG lineage. More specifically, it provides a brief introduction into plasmalemmal NCXs and their modes of activity, and it discusses the roles of OLG expressed NCXs in regulating CNS myelination and in contributing to CNS pathologies associated with detrimental effects on OLG lineage cells.

Fibroadipose Vascular Anomaly in the Upper Extremity: A Distinct Entity With Characteristic Clinical, Radiological, and Histopathological Findings.

PURPOSE: Fibroadipose vascular anomaly (FAVA) is an intramuscular vascular malformation that has been recently described as a distinct clinical entity. The clinical, radiological, and histopathological characteristics of FAVA in the upper extremity are reviewed. METHODS: This was a retrospective case series of upper-extremity FAVA lesions. RESULTS: We reviewed 19 patients with FAVA of the upper limb. Pain, stiffness, swelling, and flexion contractures were the most common presentations. Except for one lesion confined to the hand, all lesions either presented with or developed a contracture within 10 years. Ten patients underwent surgical debulking. Six required tendon transfer reconstruction and 3 necessitated a free functional muscle transfer. CONCLUSIONS: Fibroadipose vascular anomaly in the upper extremity requires an accurate diagnosis and may benefit from early referral to a multidisciplinary vascular anomaly center with experienced hand surgeons. Compression garments, propranolol, and sclerotherapy seem to be ineffective. Surgical resection focused on symptomatic regions with appropriate reconstruction may have benefit in salvage of limbs with compromised function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Surgical Management of Fibroadipose Vascular Anomaly of the Lower Extremities.

BACKGROUND: Fibroadipose vascular anomaly (FAVA) is a recently-defined vascular malformation often involving the extremities and presenting in childhood. Patients may present to orthopaedic surgeons with pain, swelling, joint contractures, and leg length discrepancy. There is no established therapy or treatment paradigm. We report on outcomes following surgical excision for patients with this condition. METHODS: Between 2007 and 2016, all 35 patients that underwent excision of lower-extremity FAVA were retrospectively reviewed using a combination of medical records, radiologic findings, and telemedicine reviews. RESULTS: Mean age at initial presentation was 12.3±6.8 years. Mean follow-up from time of definitive diagnosis at our institution was 66 months (range: 12 to 161 mo). Mean follow-up after surgery was 35 months (range: 6 to 138 mo). Females were affected more than males (71% vs. 29%). The most common location of FAVA was in the calf (49%), followed by the thigh (40%). The most commonly involved muscle was gastrocnemius (29%), followed by the quadriceps (26%). At latest follow-up after surgery, there was an improvement in the proportion of patients with pain at rest (63% vs. 29%), pain with activity (100% vs. 60%), as well as analgesia use (94% vs. 37%). Fourteen patients (40%) had symptomatic residual disease or recurrence of FAVA requiring further treatment. Six patients (17%) required further surgery and 6 (17%) required further interventional radiologic procedures. Three patients (9%) required eventual amputation for intractable pain and loss of function. Lesions with direct nerve involvement were associated with persistent neuropathic symptoms at latest follow-up (P=0.002) as well as symptomatic residual disease and/or recurrence requiring further treatment (P=0.01). Seventeen patients (49%) had 19 preoperative joint contractures. Eighteen of the 19 contractures (95%) had sustained improvement at latest follow-up. CONCLUSIONS: In carefully selected patients, surgical excision of FAVA results in improvement of symptoms. However, symptomatic residual disease and/or recurrence are not uncommon. Direct nerve involvement is associated with a worse outcome. LEVEL OF EVIDENCE: Level IV-case series.

Best practice guidelines regarding diagnosis and management of patients with type II collagen disorders.

PURPOSE: Skeletal dysplasias comprise a heterogeneous group of inherited disorders of development, growth, and maintenance of the human skeleton. Because of their relative rarity and wide phenotypic variability, patients should be accurately identified, uniformly assessed, and managed by clinicians who are aware of their potential complications and possess the knowledge and resources to treat them effectively. This study presents expert guidelines developed to improve the diagnosis and management of patients with type II collagen skeletal disorders to optimize clinical outcomes. METHODS: A panel of 11 multidisciplinary international experts in the field of skeletal dysplasia participated in a Delphi process, which comprised analysis of a thorough literature review with subsequent generation of 26 diagnosis and care recommendations, followed by two rounds of anonymous voting with an intervening face-to-face meeting. Those recommendations with more than 80% agreement were considered as consensual. RESULTS: After the first voting round, consensus was reached to support 12 of 26 (46%) statements. After the panel discussion, the group reached consensus on 22 of 24 revised statements (92%). CONCLUSIONS: Consensus-based, expert best practice guidelines developed as a standard of care to assist accurate diagnosis, minimize associated health risks, and improve clinical outcomes for patients with type II collagen skeletal dysplasias.