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Objective To characterize the incidence and prevalence of childhood‐onset systemic lupus erythematosus (SLE), and to estimate the proportion of patients who are diagnosed with SLE during childhood. Methods A cohort of patients with incident childhood‐onset SLE from 1976 to 2018 from an 8‐county region in the US were identified based on comprehensive medical record review. All patients met the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE or the ACR SLE classification criteria from 1997 at or before age 18 years. Incidence rates were estimated using Poisson methods. We estimated the childhood‐onset SLE point prevalence for January 1, 2015. Results were sex and age adjusted to the US 2000 population. Among all the SLE patients living in the 8‐county region on January 1, 2015, the proportion of patients diagnosed at ≤18 years was estimated. Results A total of 13 children were diagnosed with childhood‐onset SLE during the study period (using the EULAR/ACR definition; mean age at diagnosis 15.1 years, 85% female, 69% White). Childhood‐onset SLE overall adjusted incidence rate was 0.7 (95% confidence interval [95% CI] 0.2–1.1) per 100,000 children. The incidence rate in girls was 1.2 (95% CI 0.5–1.9) per 100,000 children, while in boys it was 0.2 (95% CI 0.0–0.5) per 100,000. The adjusted prevalence of childhood‐onset SLE was 1.1 (95% CI 0.0–3.1) per 100,000 children. The proportion of patients with SLE diagnosed as children was 9% (95% CI 6–13%). Conclusion In this population‐based study, both the incidence and prevalence rates of childhood‐onset SLE were ~1 per 100,000 children. One in 10 adults with SLE was diagnosed in childhood. More studies are needed to further characterize the epidemiology of childhood‐onset SLE in minorities.

Abstract INTRODUCTION Central nervous system (CNS) relapse is a challenging situation in diffuse large B-cell lymphoma (DLBCL). High CNS-International Prognostic Index (IPI), activated B-cell (ABC) subtype and MYD88 L265P mutation, features often found in transformed Waldenström macroglobulinemia (WM), are associated with a higher risk for developing CNS relapse. This study was aimed to describe CNS involvement in a large cohort of transformed WM. METHODS This international multicenter retrospective study included patients with a diagnosis of WM and a concurrent or sequential histological diagnosis of DLBCL. CNS disease was diagnosed by detection of DLBCL cells in the cerebrospinal fluid and/or by brain biopsy. Patients with CNS involvement by lymphoplasmacytic cells (Bing-Neel syndrome) were excluded. Of 254 identified patients with a diagnosis of histological transformation (HT) between 1988 and 2020, 19 were excluded due to lack of data on extranodal involvement. The first part of the analysis focused on baseline CNS involvement. Clinicobiological characteristics were compared between groups using Chi-square or Fisher's exact tests or Mann Whitney tests as appropriate. We analyzed CNS recurrence in the second part of the study. Forty-eight additional patients were excluded due to baseline CNS involvement (n = 25), absence of treatment at HT (n = 14) and lack of details on follow-up (n = 9). Cumulative incidence of CNS relapse was analyzed using competing-risk models that accounted for other events like systemic relapse or death from any cause, reporting sub-hazard ratio (SHR). RESULTS Baseline CNS involvement was present in 25 patients (11%) with transformed WM, including 10 (4%) with parenchymal disease, 10 with leptomeningeal, 4 (2%) with both, and 1 with unspecified CNS involvement. Characteristics associated with baseline CNS involvement were performance status 2-4 (P=0.03) and ≥2 extranodal sites (P=0.02). Median survival after HT was 1 year [0.7-2.5], comparable to the one of patients without CNS disease (1.8 year [1.2-2.6], P=0.74). We observed no difference in survival based on isolated CNS involvement (n = 10) compared to CNS and systemic involvement (n = 15) (P=0.94). Twenty-three CNS relapses occurred (12%). The 2-year and 3-year rates of CNS relapse were 9% (95% CI, 6-14) and 11% (95% CI, 7-16) (Figure 1). The median time to relapse in the CNS was 11 months (95% CI, 7-25). Thirteen CNS recurrences (57%) occurred during the first year of follow-up. Seventy percent were isolated CNS relapses. The location was leptomeningeal in 43% of cases, parenchymal in 35%, both in 17%, and unspecified in 4%. According to CNS-IPI risk groups (data available for 20 patients), 9 patients (45%) belonged to the high-risk group, 10 (50%) to the intermediate-risk group and 1 (5%) to the low-risk group. Prior to CNS relapse, 87% of patients had received rituximab, and 39% had received CNS prophylaxis (30% intrathecal chemotherapy, 4% high-dose methotrexate (HD-MTX), and 4% both). After CNS recurrence, 96% of patients received salvage treatment: combination of HD-MTX and HD-cytarabine (48%), HD-MTX alone (30%), or HD-cytarabine alone (9%). Four patients underwent consolidative autologous stem cell transplantation. The median survival after CNS relapse was 5.6 months. Factors associated with 3-year cumulative incidence of CNS recurrence in univariate analysis were involvement of kidney/adrenal glands (HR, 4.4; P=0.01) and MYD88 L265P mutation (P=0.01) (Figure 2A and B). Of note, among 74 patients (over 187, 40%) with data available for MYD88 mutation status, 11 CNS relapses occurred in patients with MYD88 L265P mutation (n = 54, 20%) whereas no relapse were observed in MYD88 WT cohort (n = 20). A trend toward higher risk of CNS relapse for ≥2 extranodal sites (HR, 2.3, 95% CI 0.98-5.3; P=0.06) was observed. Cumulative incidence according to CNS-IPI risk groups (0% in the low-risk, 9% in the intermediate-risk and 14% in the high-risk group) was not statistically significant (P=0.47). CONCLUSION CNS involvement occurs frequently in transformed WM. Rate of CNS relapse seems similar to DLBCL patients belonged to the CNS-IPI high-risk group. Special attention should be paid to patients with kidney/adrenal involvement and MYD88 L265P mutation. Figure 1 Figure 1. Disclosures Vos: Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel reimbursement. Treon: X4: Research Funding; Janssen: Consultancy, Research Funding; Dana Farber Cancer Institute: Current Employment; BMS: Consultancy, Research Funding; Self: Patents & Royalties: Holder of multiple patents related to testing and treatment of MYD88 and CXCR4 mutated B-cell malignancies; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Dimopoulos: Janssen: Honoraria; Beigene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Takeda: Honoraria. Kapoor: Cellectar: Consultancy; Karyopharm: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Background: Athletes of all sports often have shoulder instability, most commonly as anterior shoulder instability (ASI). For overhead athletes (OHAs) and those participating in throwing sports, clinical and surgical decision making can be difficult owing to a lack of long-term outcome studies in this population of athletes. Purpose/Hypothesis: To report presentation characteristics, pathology, treatment strategies, and outcomes of ASI in OHAs and throwers in a geographic cohort. We hypothesized that OHAs and throwers would have similar presenting characteristics, management strategies, and clinical outcomes but lower rates of return to play (RTP) when compared with non-OHAs (NOHAs) and nonthrowers, respectively. Study Design: Cohort study; Level of evidence, 3. Methods: An established geographic medical record system was used to identify OHAs diagnosed with ASI in the dominant shoulder. An overall 57 OHAs with ASI were matched 1:2 with 114 NOHAs with ASI. Of the OHAs, 40 were throwers. Sports considered overhead were volleyball, swimming, racquet sports, baseball, and softball, while baseball and softball composed the thrower subgroup. Records were reviewed for patient characteristics, type of sport, imaging findings, treatment strategies, and surgical details. Patients were contacted to collect Western Ontario Shoulder Instability index (WOSI) scores and RTP data. Statistical analysis compared throwers with nonthrowers and OHAs with NOHAs. Results: Four patients, 3 NOHAs and 1 thrower, were lost to follow-up at 6 months. Clinical follow-up for the remaining 167 patients (98%) was 11.9 ± 7.2 years (mean ± SD). Of the 171 patients included, an overall 41 (36%) NOHAs, 29 (51%) OHAs, and 22 (55%) throwers were able to be contacted for WOSI scores and RTP data. OHAs were more likely to initially present with subluxations (56%; P = .030). NOHAs were more likely to have dislocations (80%; P = .018). The number of instability events at presentation was similar. OHAs were more likely to undergo initial operative management. Differences in rates of recurrent instability were not significant after initial nonoperative management (NOHAs, 37.1% vs OHAs, 28.6% [ P = .331] and throwers, 21.2% [ P = .094]) and surgery (NOHAs, 20.5% vs OHAs, 13.0% [ P = .516] and throwers, 9.1% [ P = .662]). Rates of revision surgery were similar (NOHAs, 18.0% vs OHAs, 8.7% [ P = .464] and throwers, 18.2% [ P > .999]). RTP rates were 80.5% in NOHAs, as compared with 71.4% in OHAs ( P = .381) and 63.6% in throwers ( P = .143). Median WOSI scores were 40 for NOHAs, as compared with 28 in OHAs ( P = .425) and 28 in throwers ( P = .615). Conclusion: In a 1:2 matched comparison of general population athletes, throwers and OHAs were more likely to have more subtle instability, as evidenced by higher rates of subluxations rather than frank dislocations, when compared with NOHAs. Despite differences in presentation and the unique sport demands of OHAs, rates of recurrent instability and revision surgery were similar across groups. Similar outcomes in terms of RTP, level of RTP, and WOSI scores were achieved for OHAs and NOHAs, but these results must be interpreted with caution given the limited sample size.

Objectives: There is a paucity of literature regarding outcomes of anterior shoulder instability (ASI) in throwers and overhead athletes (OHA). The purpose of this study was to report the pathology, treatment strategies, and outcomes of ASI in throwers and overhead athletes utilizing an established US geographic population-based cohort. Methods: An established geographic database of more than 500,000 patients was used to identify athletes <40 years of age with ASI between 1994 and 2016. Medical records were reviewed to obtain demographics, type of sport, surgical details, and clinical outcomes. Patients were contacted after final clinical follow-up for patient reported outcomes (PRO). The Western Ontario Shoulder Instability (WOSI) score, return to sport at previous level of performance (RPP), rate of return to play (RTP) and time to RTP were recorded. Statistical analysis was performed comparing throwers to non-throwers and OHA to non-overhead athletes (NOHA). Results: The study population consisted of 171 patients, 114 NOHA and 57 OHA. Of the OHA, 40 were throwers. The mean follow-up was 14.7 ± 5.6 years for PRO’s and 11.7 ± 7.3 years for last clinical evaluation. No difference in overall instability events was seen in either group. Throwers were more likely to present with subluxations while non-throwers were more likely to present with frank dislocations. NOHA and non-throwers were more likely than OHA and throwers to have a history of trauma related to ASI, respectively ( P = <.001, P = .002). Throwers were more likely to undergo an open surgical procedure (45%) than non-throwers (15%) ( P = .038). The rate of recurrent instability between groups was similar. Throwers returned to sport at a lower rate than non-throwers, however this did not reach significance (64% vs 83%, P = .100). Throwers and OHA reported similar WOSI scores, RPP and time to RTP grouped by surgical or conservative management compared to non-throwers and NOHA, respectively. Conclusions: In a US cohort of patients, throwers and OHA had a similar number of instability events compared to non-throwers and NOHA, respectively. Non-throwers and NOHA were more likely to present with frank dislocation which is supported by the significantly higher rates of trauma in both groups. Notably, the WOSI score, RPP, rate of RTP and time to RTP showed no difference between throwers and OHA when compared to their non-throwing and NOHA counterparts.

AbstractObjectiveTo estimate the incidence and time-to-classification of SLE by the 1997 ACR (ACR97) criteria, the SLICC criteria, and the European Alliance of Associations for Rheumatology/ACR (EULAR/ACR) criteria.MethodsWe identified all incident SLE cases from 2000–2018 in the well-defined Olmsted County population. Clinical data included in the ACR97, SLICC and EULAR/ACR criteria were manually abstracted from medical records. All incident cases met at least one of the three classification criteria. Time-to-classification was estimated from the first documented lupus-attributable disease manifestation to the time of criteria fulfilment by each of the three definitions. Annual incidence rates were age or age/sex adjusted to the 2000 US population.ResultsOf 139 incident cases there were 126 cases by the EULAR/ACR criteria, corresponding to an age/sex-adjusted incidence of 4.5 per 100 000 population (95% CI: 3.7, 5.2). The age/sex-incidence was higher than that of the SLICC criteria (113 cases; 4.0 per 100 000 [95% CI: 3.3, 4.7], P = 0.020) and the ACR97 (92 cases; 3.3 per 100 000 [95% CI: 2.6, 3.9], P &lt; 0.001). The median time from first disease manifestation to criteria fulfilment was shorter for the EULAR/ACR criteria (29.4 months) than the ACR97 criteria (47.0 months, P &lt; 0.001) and similar to the SLICC criteria (30.6 months, P = 0.83).ConclusionThe incidence of SLE was higher by the EULAR/ACR criteria compared with the ACR97 and the SLICC criteria, and the EULAR/ACR criteria classified patients earlier that the ACR97 criteria but similar to the SLICC criteria.

Abstract Background:The standard of care for elderly glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions.Methods:Elderly patients (≥ 65 years old) who received hypofractionated radiation with TMZ from 2010-2020 were included in this analysis. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared between patients who received 40 Gy and 52.5 Gy. Univariable and multivariable analyses were performed.Results: Sixty-six newly diagnosed patients were eligible for analysis. Thirty-nine patients were treated with 40 Gy in 15 fractions while twenty-seven were treated with 52.5 Gy in 15 fractions. Patients had no significant differences in age, sex, methylation status, or performance status. Overall survival (OS) was superior in the 52.5 Gy group (14.1 months) when compared to the 40 Gy group (7.9 months, p = 0.011). Isoeffective dosing to 52.5 Gy was shown to be an independent prognostic factor for improved OS on multivariable analysis. Conclusions:Isoeffective dosing to 52.5 Gy in 15 fractions was associated with superior OS compared to standard of care 40 Gy in 15 fractions. These hypothesis generating data support accelerated hypofractionation in future prospective trials.

Purpose Clinical trials have demonstrated that standardized voice treatment programs are effective for some patients, but identifying the unique individual treatment ingredients specifically responsible for observed improvements remains elusive. To address this problem, the authors used a taxonomy of voice therapy, the Rehabilitation Treatment Specification System (RTSS), and a Delphi process to develop the RTSS-Voice (expert consensus categories of measurable and unique voice treatment ingredients and targets). Method Initial targets and ingredients were derived from a taxonomy of voice therapy. Through six Delphi Rounds, 10 vocal rehabilitation experts rated the measurability and uniqueness of individual treatment targets and ingredients. After each round, revisions (guided by the experts' feedback) were finalized among a primary reader (a voice therapy expert) and two external readers (rehabilitation experts outside the field of voice). Consensus was established when the label and definition of an ingredient or target reached a supramajority threshold (≥ 8 of 10 expert agreement). Results Thirty-five target and 19 ingredient categories were agreed to be measurable, unique, and accurate reflections of the rules and terminology of the RTSS. Operational definitions for each category included differences in the way ingredients are delivered and the way individual targets are modified by those ingredients. Conclusions The consensus labels and operationalized ingredients and targets making up the RTSS-Voice have potential to improve voice therapy research, practice, and education/training. The methods used to develop these lists may be useful for other speech, language, and hearing treatment specifications. Supplemental Material https://doi.org/10.23641/asha.15243357

ABSTRACT We measured the passive mechanical properties of intact, living human gracilis muscles (n=11 individuals, 10 male and 1 female, age: 33±12 years, mass: 89±23 kg, height: 177±8 cm). Measurements were performed in patients undergoing surgery for free-functioning myocutaneous tissue transfer of the gracilis muscle to restore elbow flexion after brachial plexus injury. Whole-muscle force of the gracilis tendon was measured in four joint configurations (JC1–JC4) with a buckle force transducer placed at the distal tendon. Sarcomere length was also measured by biopsy from the proximal gracilis muscle. After the muscle was removed, a three-dimensional volumetric reconstruction of the muscle was created via photogrammetry. Muscle length from JC1 to JC4 increased by 3.3±1.0, 7.7±1.2, 10.5±1.3 and 13.4±1.2 cm, respectively, corresponding to 15%, 34%, 46% and 59% muscle fiber strain, respectively. Muscle volume and an average optimal fiber length of 23.1±0.7 cm yielded an average muscle physiological cross-sectional area of 6.8±0.7 cm2 which is approximately 3 times that measured previously from cadaveric specimens. Absolute passive tension increased from 0.90±0.21 N in JC1 to 16.50±2.64 N in JC4. As expected, sarcomere length also increased from 3.24±0.08 µm at JC1 to 3.63±0.07 µm at JC4, which are on the descending limb of the human sarcomere length–tension curve. Peak passive muscle stress was 27.8±5.5 kPa in JC4 and muscle modulus ranged from 44.8 MPa in JC1 to 125.7 MPa in JC4. Comparison with other mammalian species indicates that human muscle passive mechanical properties are more similar to rodent muscle than to rabbit muscle. These data provide direct measurements of whole-human muscle passive mechanical properties that can be used in modeling studies and for understanding comparative passive mechanical properties among mammalian muscles.