Sex-Related Differences in Shoulder Complex Joint Dynamics Variability During Pediatric Manual Wheelchair Propulsion.

More than 80% of adult manual wheelchair users with spinal cord injuries will experience shoulder pain. Females and those with decreased shoulder dynamics variability are more likely to experience pain in adulthood. Sex-related differences in shoulder dynamics variability during pediatric manual wheelchair propulsion may influence the lifetime risk of pain. We evaluated the influence of sex on 3-dimensional shoulder complex joint dynamics variability in 25 (12 females and 13 males) pediatric manual wheelchair users with spinal cord injury. Within-subject variability was quantified using the coefficient of variation. Permutation tests evaluated sex-related differences in variability using an adjusted critical alpha of P = .001. No sex-related differences in sternoclavicular or acromioclavicular joint kinematics or glenohumeral joint dynamics variability were observed (all P ≥ .042). Variability in motion, forces, and moments are considered important components of healthy joint function, as reduced variability may increase the likelihood of repetitive strain injury and pain. While further work is needed to generalize our results to other manual wheelchair user populations across the life span, our findings suggest that sex does not influence joint dynamics variability in pediatric manual wheelchair users with spinal cord injury.

Teprotumumab for the Treatment of Active Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).

A multicenter study to evaluate pain characteristics in osteogenesis imperfecta.

The objective was to describe pain characteristics and treatments used in individuals with varying severity of osteogenesis imperfecta (OI) and investigate pain-associated variables. This work was derived from a multicenter, longitudinal, observational, natural history study of OI conducted at 12 clinical sites of the NIH Rare Diseases Clinical Research Network's Brittle Bone Disorders Consortium. Children and adults with a clinical, biochemical, or molecular diagnosis of OI were enrolled in the study. We did a cross-sectional analysis of chronic pain prevalence, characteristics, and treatments used for pain relief and longitudinal analysis to find the predictors of chronic pain. We included 861 individuals with OI, in 41.8% chronic pain was present, with similar frequency across OI types. Back pain was the most frequent location. Nonsteroidal anti-inflammatory drugs followed by bisphosphonates were the most common treatment used. Participants with chronic pain missed more days from school or work/year and performed worse in all mobility metrics than participants without chronic pain. The variables more significantly associated with chronic pain were age, sex, positive history of rodding surgery, scoliosis, other medical problems, assistive devices, lower standardized height, and higher body mass index. The predictors of chronic pain for all OI types were age, use of a wheelchair, and the number of fractures/year. Chronic pain is prevalent in OI across all OI types, affects mobility, and interferes with participation. Multiple covariates were associated with chronic pain.

Necrobiotic Xanthogranuloma With Associated Monoclonal Gammopathy Presenting as an Eyelid Nodule.

Necrobiotic xanthogranuloma (NXG) is a progressive non-Langerhans cell histiocytosis with a predilection for the periorbital area. NXG is most commonly associated with monoclonal gammopathy and ophthalmic complications. The authors present a 69-year-old man who was evaluated for a left upper eyelid nodule and plaques on the lower extremities, trunk, abdomen, and right upper extremity. Biopsy of the eyelid was supportive for NXG. Serum protein electrophoresis was positive for a monoclonal gammopathy, IgG light chain kappa. MRI showed preseptal involvement. The periocular nodules cleared with a high dose of prednisone; however, the other skin lesions persisted. Bone marrow biopsy showed kappa-restricted 6% plasma cells and he was treated with intravenous immunoglobulin. This case illustrates the importance of clinicopathologic correlations to render an NXG diagnosis.

Inflammation and Fibrosis in Orbital Inflammatory Disease: A Histopathologic Analysis.

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens. METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls. RESULTS: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048). CONCLUSIONS: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease.

Relationships Among Shoulder Rotational Strength, Range of Motion, Pitching Kinetics, and Pitch Velocity in Collegiate Baseball Pitchers.

ABSTRACT: Cross, JA, Higgins, AW, Dziuk, CC, Harris, GF, and Raasch, WG. Relationships among shoulder rotational strength, range of motion, pitching kinetics, and pitch velocity in collegiate baseball pitchers. J Strength Cond Res 37(1): 129-135, 2023-Throwing shoulder injuries are the most common type of injury experienced by baseball pitchers. Weakness in the shoulder musculature and insufficient throwing arm range of motion are both risk factors for developing a shoulder injury. The goal of this study was to determine correlations among shoulder rotational strength, range of motion, pitching kinetics, and pitch velocity in collegiate pitchers. Thirteen uninjured male college pitchers were evaluated. Clinical measures included shoulder internal and external rotation range of motion, peak isokinetic internal and external rotator strength, and peak isometric internal and external rotator strength. Three-dimensional biomechanics were assessed as subjects threw from an indoor pitching mound to a strike zone net at regulation distance. Pearson's correlations were used to assess the associations among the clinical measures and throwing metrics. Five significant correlations were found between peak shoulder compressive force and strength, and 4 significant correlations were found between pitching velocity and strength ( p < 0.05). No significant correlations were found between range of motion and pitching kinetics or velocity. Our results suggest that as shoulder rotational strength increases, the peak shoulder compressive force and pitch velocity both increase. Knowledge of relationships between strength metrics and pitching biomechanics may allow for improved strength training routines with the goal of increasing velocity without increasing injury risk.

Orbital MALT lymphoma with amyloid deposition.

MALT lymphoma is a commonly encountered orbital tumor, and primary amyloidosis is frequently found to be an independent orbital lesion. Orbital MALT lymphoma with associated amyloid deposition is considered rare, with only 12 cases previously published. We describe a 33-year-old man, the youngest patient reported to-date, with a mass in the superonasal quadrant of the right anterior orbit. Pathology demonstrated extranodal marginal zone lymphoma in mucosa-associated lymphoid tissue with associated amyloid deposition. Systemic work-up revealed no other site of either lymphoma or amyloidosis. The patient underwent local irradiation and subsequent surgical resection of the residual mass. Persistent lymphoma was found and treated with rituximab.

Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study.

PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.

Ocular Ultrasound: Review of Bioeffects and Safety, Including Fetal and Point of Care Perspective: Review of Bioeffects and Safety, Including Fetal and Point-of-Care Perspective.

Ocular ultrasound is an invaluable tool for the evaluation of the eye and orbit. However, the eye and orbit are potentially sensitive to the thermal and mechanical effects of ultrasound. When performing B-mode imaging, dedicated ocular settings should be used. If these settings are not available, limiting the acoustic output to Food and Drug Administration (FDA) recommended maximum levels is strongly advised. Especially important is the acoustic output in spectral (pulsed) and color Doppler modes, which can exceed the FDA's maximum recommended levels for the eye. Adjusting settings to decrease acoustic output and limiting the time of the examination should be done when performing a Doppler examination. The acoustic output of shear wave elastography is significantly higher than FDA guidelines for the eye and should be considered experimental.

Management of periocular cutaneous squamous cell carcinoma with perineural invasion: a case series and literature review.

PURPOSE: To review and elucidate the complex, multimodal management of periocular cutaneous squamous cell carcinoma (SCC) with perineural invasion (PNI), and offer practical, evidence-based patient care recommendations. METHODS: Three exemplary cases of high-risk periocular cutaneous SCC with PNI were selected from a single surgeon's experience. The clinical courses, management, and clinical outcomes, with follow-up intervals of 19, 19, and 24 months after presentation, were reviewed. The English-language literature on PNI, with attention to the management of cutaneous SCC of the head and neck (SCCHN), was reviewed. RESULTS: PNI of cutaneous SCCHN portends aggressive tumor behavior and a worsened prognosis. Treatment is multimodal, with varied combinations of surgical excision, radiotherapy (RT), and systemic chemotherapy. Retrospective reports from multiple institutions involve heterogenous patient populations, treatment strategies, and confounding variables that preclude formulation of a standardized treatment paradigm. Newer, comparative studies of advanced RT techniques (e.g., hyper-fractionation), novel systemic chemotherapeutic agents (e.g., cetuximab, cemiplimab), and varied integrative regimens are providing additional insights. Prompt initiation of adjuvant therapies (within 6-8 weeks of surgery), and careful evaluation of lymphatic basins can increase oncologic control. Utilizing deep-tissue fixation of advancement flaps and eyelid stabilization can enhance functional and aesthetic results. CONCLUSIONS: Management of cutaneous SCC with PNI remains complex and in most cases requires combined-modality therapy directed by a multidisciplinary tumor board. With novel therapies and new treatment patterns, optimal combinations and intensities of individual modalities require further elucidation. The oculofacial plastic surgeon plays a pivotal role - in diagnosis, coordination of interdisciplinary management, thoughtful surgical reconstruction, and postoperative surveillance.

Geographic clustering of cutaneous T-cell lymphoma in New Jersey: an exploratory analysis using residential histories.

PURPOSE: Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma. Previous studies have reported geographic clustering of CTCL based on the residence at the time of diagnosis. We explore geographic clustering of CTCL using both the residence at the time of diagnosis and past residences using data from the New Jersey State Cancer Registry. METHODS: CTCL cases (n = 1,163) diagnosed between 2006-2014 were matched to colon cancer controls (n = 17,049) on sex, age, race/ethnicity, and birth year. Jacquez's Q-Statistic was used to identify temporal clustering of cases compared to controls. Geographic clustering was assessed using the Bernoulli-based scan-statistic to compare cases to controls, and the Poisson-based scan-statisic to compare the observed number of cases to the number expected based on the general population. Significant clusters (p < 0.05) were mapped, and standard incidence ratios (SIR) reported. We adjusted for diagnosis year, sex, and age. RESULTS: The Q-statistic identified significant temporal clustering of cases based on past residences in the study area from 1992 to 2002. A cluster was detected in 1992 in Bergen County in northern New Jersey based on the Bernoulli (1992 SIR 1.84) and Poisson (1992 SIR 1.86) scan-statistics. Using the Poisson scan-statistic with the diagnosis location, we found evidence of an elevated risk in this same area, but the results were not statistically significant. CONCLUSION: There is evidence of geographic clustering of CTCL cases in New Jersey based on past residences. Additional studies are necessary to understand the possible reasons for the excess of CTCL cases living in this specific area some 8-14 years prior to diagnosis.

Case Report: Idiopathic Sclerosing Orbital Inflammation.

SIGNIFICANCE: Idiopathic sclerosing orbital inflammation (ISOI) is characterized by insidious, chronic, progressive inflammation and fibrosis that damage ocular structures and produce a mass effect. This case highlights the challenges in diagnosis and management of ISOI, as well as the associated ocular morbidities, including potential vision loss. PURPOSE: The purpose of this study was to provide education regarding a rare condition that exhibits variable presentation and has an unpredictable success rate with regard to treatment paradigm. Improved therapeutic options are promising. Ultimately, early detection and management are key and may allow for better visual outcome. CASE REPORT: A 46-year-old woman presented with complaints of chronic right-sided facial headaches and eye pain and gradual right globe prominence over the previous 6 months. Worsening vision and decreased right peripheral visual field were also noted. Upon examination, an afferent pupillary defect and florid disc edema were evident. Imaging studies revealed an orbital and extraorbital infiltrative mass involving the right orbital apex, inferior orbital fissure, pterygopalatine fossa, and cavernous sinus. Right anterior orbitotomy with biopsy revealed fragments of fibroconnective and adipose tissue with sclerosis and chronic focal inflammation, consistent with ISOI. Treatment included intravenous methylprednisone, followed by oral prednisone, beginning at 60 mg/d with a slow taper thereafter. Signs and symptoms improved dramatically and eventually resolved. Vision significantly improved, and the afferent pupillary defect resolved. The patient remained asymptomatic at 3-month follow-up. CONCLUSIONS: Idiopathic sclerosing orbital inflammation is difficult to diagnose and manage. No large studies exist because of the rare nature of the disease. Slowly progressive, nonspecific signs and symptoms may delay recognition and treatment. Orbital imaging and histopathologic analysis are critical for definitive diagnosis. Conventional treatment with corticosteroids is not uniformly successful, but newer combined therapy options can improve outcomes. Early identification and treatment are key to management and ultimate preservation of function and vision.

Teprotumumab in Clinical Practice: Recommendations and Considerations From the OPTIC Trial Investigators.

BACKGROUND: Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials. METHODS: An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on. RESULTS: The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab. CONCLUSIONS: Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.

Fate and Management of Incompletely Excised Solitary Fibrous Tumor of the Orbit: A Case Series and Literature Review.

PURPOSE: There is an imperfect correlation between the histology and behavior of solitary fibrous tumor (SFT). In addition, recurrence is common, and dedifferentiation may occur over time. Preferred primary treatment is intact excision, but friable pseudocapsules and tenacious attachments can thwart this goal in the crowded, visually sensitive orbit. This study addresses the fate and appropriate management of incompletely excised orbital SFT. METHODS: Among a single surgeon's 7-case experience with orbital SFT, 3 cases involved incomplete primary excision, either before (2 cases) or after (1 case) referral. We reviewed the clinicopathologic data in these 3 cases, with follow-up intervals of 18, 21, and 52 years after initial presentation. We reviewed the English-language literature on SFT, with special attention to evolving nomenclature, orbital involvement, recurrence, malignant transformation, and management options. RESULTS: Benign versus malignant designations of SFT vary with histological and behavioral criteria. Approximately 150 orbital cases have been reported. Published rates of primary malignancy and recurrence across all histologic categories are 6% to 12% and 30% to 37%, respectively. We identified 43 well-documented recurrences (range, 6 months-33 years; median, 3 years) and 10 cases of histological dedifferentiation (range, 14 months-33 years). Because of SFT's rarity and needed follow-up intervals, the value of adjuvant therapy is not yet proven. In follow up of 18, 21, and 52 years after initial presentation, our 3 cases with incomplete excision showed either no recurrence (Case 1) or no morphological dedifferentiation (Cases 2, 3). CONCLUSION: A treatment algorithm is predicated on the completeness of surgical excision and histological features. However, we recommend case-by-case multidisciplinary decisions in a tumor-board setting.

Teprotumumab for Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).

Pediatric Outcomes Data Collection Instrument is a Useful Patient-Reported Outcome Measure for Physical Function in Children with Osteogenesis Imperfecta.

PURPOSE: Patient-reported outcome measures (PROMs) are increasingly recognized as valuable endpoints in clinical trials. The Pediatric Outcomes Data Collection Instrument (PODCI) is a PROM utilized in children with musculoskeletal disorders. We evaluated the validity and reliability of PODCI in children with osteogenesis imperfecta (OI). METHODS: Physical functioning and psychological well-being were assessed using PODCI in a large cohort of children enrolled in a multicenter study conducted by the Brittle Bone Disorders Consortium. Physical function scores were correlated with a validated, observer-rated scale, Brief Assessment of Motor Function (BAMF), and with psychological well-being scores. We calculated sample sizes required to detect clinically meaningful differences in physical function. RESULTS: Four hundred seventeen children with OI types I, III, and IV were enrolled. Physical function scores in OI type III were significantly lower than those in OI types I and IV. There were no significant differences in psychological well-being. PODCI physical function scores showed moderate-to-strong correlation with BAMF. The Global Functioning Scale, a composite of physical function, did not consistently correlate with psychological well-being. CONCLUSION: PODCI can be a reliable measure of physical functioning in children with OI and offers valuable information about patient-reported health status and new ways to examine the utility of interventions in this population.

Socioeconomic Disparities in Colon Cancer Survival: Revisiting Neighborhood Poverty Using Residential Histories.

BACKGROUND: Residential histories linked to cancer registry data provide new opportunities to examine cancer outcomes by neighborhood socioeconomic status (SES). We examined differences in regional stage colon cancer survival estimates comparing models using a single neighborhood SES at diagnosis to models using neighborhood SES from residential histories. METHODS: We linked regional stage colon cancers from the New Jersey State Cancer Registry diagnosed from 2006 to 2011 to LexisNexis administrative data to obtain residential histories. We defined neighborhood SES as census tract poverty based on location at diagnosis and across the follow-up period through 31 December 2016 based on residential histories (average, time-weighted average, time-varying). Using Cox proportional hazards regression, we estimated associations between colon cancer and census tract poverty measurements (continuous and categorical), adjusted for age, sex, race/ethnicity, regional substage, and mover status. RESULTS: Sixty-five percent of the sample was nonmovers (one census tract); 35% (movers) changed tract at least once. Cases from tracts with >20% poverty changed residential tracts more often (42%) than cases from tracts with <5% poverty (32%). Hazard ratios (HRs) were generally similar in strength and direction across census tract poverty measurements. In time-varying models, cases in the highest poverty category (>20%) had a 30% higher risk of regional stage colon cancer death than cases in the lowest category (<5%) (95% confidence interval [CI] = 1.04, 1.63). CONCLUSION: Residential changes after regional stage colon cancer diagnosis may be associated with a higher risk of colon cancer death among cases in high-poverty areas. This has important implications for postdiagnostic access to care for treatment and follow-up surveillance. See video abstract: http://links.lww.com/EDE/B705.

Do Bisphosphonates Alleviate Pain in Children? A Systematic Review.

PURPOSE OF REVIEW: The goal of this systematic review is to analyze the effectiveness of bisphosphonates (BPs) to treat bone pain in children and adolescents who have diseases with skeletal involvement. RECENT FINDINGS: We included 24 studies (2 randomized controlled trials, 3 non-randomized controlled trials, 10 non-randomized open-label uncontrolled studies, 8 retrospective studies, and 1 study with design not specified). The majority of included studies assessed pain from a unidimensional approach, with pain intensity the most frequently evaluated dimension. Only 38% of studies used validated tools; visual analogue scale was the most frequently employed. BPs were used to alleviate bone pain in a wide variety of pediatrics conditions such as osteogenesis imperfecta, secondary osteoporosis, osteonecrosis related to chemotherapy, chronic non-bacterial osteitis, idiopathic juvenile osteoporosis, unresectable benign bone tumor, and cancer-related pain. Twenty of the 24 studies reported a positive effect of BPs for alleviating pain in different pathologies, but 58% of the studies were categorized as having high risk of bias. Intravenous BPs are helpful in alleviating bone pain in children and adolescents. It is advised that our results be interpreted with caution due to the heterogeneity of the doses used, duration of treatments, and types of pathologies included. In addition, this review shows the paucity of high-quality evidence in the available literature and further research is needed. TRIAL REGISTRATION: Before the completion of this review, the protocol was registered to PROSPERO (International prospective register of systematic reviews), PROSPERO 2020 ID # CRD42020158316. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020158316.

Diagnostic Ultrasound Safety Review for Point-of-Care Ultrasound Practitioners.

Potential ultrasound exposure safety issues are reviewed, with guidance for prudent use of point-of-care ultrasound (POCUS). Safety assurance begins with the training of POCUS practitioners in the generation and interpretation of diagnostically valid and clinically relevant images. Sonographers themselves should minimize patient exposure in accordance with the as-low-as-reasonably-achievable principle, particularly for the safety of the eye, lung, and fetus. This practice entails the reduction of output indices or the exposure duration, consistent with the acquisition of diagnostically definitive images. Informed adoption of POCUS worldwide promises a reduction of ionizing radiation risks, enhanced cost-effectiveness, and prompt diagnoses for optimal patient care.

The spectrum of orbital dermoid cysts and their surgical management.

PURPOSE: The purpose of this study is to describe a spectrum of surgical approaches to orbital dermoid cysts, influenced by the anatomic location of the expanded cyst wall and other factors. METHODS: In this retrospective case series, we reviewed cases of dermoid cysts surgically excised during a 39-year period (1977-2016). Cysts were categorized according to the location of the expanded cyst wall and other considerations. The impact of these factors on surgical management was determined. RESULTS: We identified six dermoid cyst growth patterns based on the anatomic location of the expanded cyst wall that influence the surgical approach: anterior to the frontozygomatic suture (FZS), superior to the FZS, medial to the FZS and other lateral wall sutures, traversing the FZS and other lateral wall sutures, nasoglabellar, and sinus tract from the orbit to the skin. Two additional factors influencing surgical methodology included satellite inflammatory pseudocysts and recurrence after surgical resection. CONCLUSION: Orbital dermoid cysts are not monolithic lesions. Functional and aesthetic outcomes can benefit from considering the anatomic pattern of cyst wall expansion and other factors in their surgical management.