Definition of Tweener: Consensus Among Experts in Treating Early-onset Scoliosis.

BACKGROUND: The term "Tweener" is colloquially used to refer to early-onset scoliosis (EOS) patients whose age and development make them candidates for multiple surgical options. The purpose of this study was to establish expert consensus on a definition to formally characterize the Tweener population. METHODS: A 3-round survey of surgeons in an international EOS study group was conducted. Surgeons were provided with various patient characteristics and asked if each was part of their definition for Tweener patients. Responses were analyzed for consensus (≥70%), near-consensus (60% to 69%), and no consensus (<60%). RESULTS: Consensus was reached (89% of respondents) for including chronological age in the Tweener definition; 8 to 10 years for females and 9 to 11 years for males. Surgeons agreed for inclusion of Sanders score, particularly Sanders 2 (86.0%). Patients who have reached Sanders 4, postmenarche, or have closed triradiate cartilage should not be considered Tweeners. Bone age range of 8 years and 10 months to 10 years and 10 months for females (12 y for males) could be part of the Tweener definition. CONCLUSIONS: This study suggests that the Tweener definition could be the following: patients with open triradiate cartilage who are not postmenarche and have not reached Sanders 4, and if they have one of the following: Sanders 2 or chronological age 8 to 10 years for females (9 to 11 y for males) or bone age 8 years and 10 months to 10 years and 10 months for females (12 y for males). This definition will allow for more focused and comparative research on this population. LEVEL OF EVIDENCE: Level V-expert opinion.

Comparative Effectiveness of a Complex Care Program for High-Cost/High-Need Patients: a Retrospective Cohort Study.

BACKGROUND: High-cost/high-need (HCHN) adults and the healthcare systems that provide their care may benefit from a new patient-centered model of care involving a dedicated physician and nurse team who coordinate both clinical and social services for a small patient panel. OBJECTIVE: Evaluate the impact of a Complex Care Program (CCP) on likelihood of patient survival and hospital admission in 180 days following empanelment to the CCP. DESIGN: Retrospective cohort study using a quasi-experimental design with CCP patients propensity score matched to a concurrent control group of eligible but unempaneled patients. SETTING: Kaiser Permanente Mid-Atlantic States (KPMAS) during 2017-2018. PARTICIPANTS: Nine hundred twenty-nine CCP patients empaneled January 2017-June 2018, 929 matched control patients for the same period. INTERVENTIONS: The KPMAS CCP is a new program consisting of 8 teams each staffed by a physician and nurse who coordinate care across a continuum of specialty care, tertiary care, and community services for a panel of 200 patients with advanced clinical disease and recent hospitalizations. MAIN OUTCOMES: Time to death and time to first hospital admission in the 180 days following empanelment or eligibility. RESULTS: Compared to matched control patients, CCP patients had prolonged time to death (hazard ratio [HR]: 0.577, 95% CI: 0.474, 0.704), and CCP decedents had longer survival (median days 69.5 vs. 53.0, p=0.03). CCP patients had similar time to hospital admission (HR: 1.081, 95% CI: 0.930, 1.258), with similar results when adjusting for competing risk of death (HR: 1.062, 95% CI: 0.914, 1.084). LIMITATIONS: Non-randomized intervention; single healthcare system; patient eligibility limited to specific conditions. CONCLUSION: The KPMAS CCP was associated with significantly reduced short-term mortality risk for eligible patients who volunteered to participate in this intervention.

A Novel Large Scale Integrated Telemonitoring Program for COVID-19.

Introduction: Coronavirus disease 2019 (COVID-19) has forced health care systems to rethink the optimal delivery of health care services and has dramatically increased demand for general medicine providers (internal medicine, family medicine, emergency medicine), while simultaneously reducing demand for many subspecialty services. At Kaiser Permanente, we implemented a program wherein health care providers drawn from multiple disciplines perform daily telemedicine check-ins on COVID-19 patients, allowing us to both maintain social distancing and make use of providers in specialties who otherwise may have had lower in-clinic volumes. Methods: Kaiser Permanente patients testing positive for COVID-19 between March and October 2020 were referred to our program. Physicians and nurses (RNs) were invited to participate in our program and were trained using Microsoft Teams™ meetings. Patients receive daily phone calls by a physician or RN. Select patients receive portable pulse oximeter devices based on standardized criteria incorporating age and comorbidities. When patients are determined to be clinically stable, they are discharged back to their primary care physician for ongoing management. Results: Descriptive results for the virtual home care program (VHCP) are reported through October 2020, though these results do not represent a planned statistical analysis. Forty-two percent of the patients were male, 43% were black, and 30% were Hispanic. The most common comorbidities of patients in our program were obesity (body mass index >30 kg/m2; 35%), followed by hypertension (32%) and diabetes mellitus (19%). Then, 8.2% of patients ultimately required hospital admission. Mortality rate for patients in our program was 1.33%. Discussion: Our program was able to provide virtual care for thousands of COVID-19 positive Kaiser members in the Washington, DC, and Baltimore Metro regions. We did so by utilizing physicians and RNs from specialties experiencing a decrease in clinic volume attributable to the COVID-19 pandemic. The experiences of our program may be valuable to clinicians wishing to establish similar programs of their own.

Characterizing Use of Growth-friendly Implants for Early-onset Scoliosis: A 10-Year Update.

BACKGROUND: Growth-friendly treatment of early-onset scoliosis (EOS) has changed with the development and evolution of multiple devices. This study was designed to characterize changes in the use of growth-friendly implants for EOS from 2007 to 2017. METHODS: We queried the Pediatric Spine Study Group database for patients who underwent index surgery with growth-friendly implants from July 2007 to June 2017. In 1298 patients, we assessed causes of EOS; preoperative curve magnitude; age at first surgery; patient sex; construct type; lengthening interval; incidence of "final" fusion for definitive treatment; and age at definitive treatment. α=0.05. RESULTS: From 2007 to 2017, the annual proportion of patients with idiopathic EOS increased from 12% to 33% (R=0.58, P=0.006). Neuromuscular EOS was the most common type at all time points (range, 33% to 44%). By year, mean preoperative curve magnitude ranged from 67 to 77 degrees, with no significant temporal changes. Mean (±SD) age at first surgery increased from 6.1±2.9 years in 2007 to 7.8±2.5 years in 2017 (R=0.78, P<0.001). As a proportion of new implants, magnetically controlled growing rods increased from <5% during the first 2 years to 83% in the last 2 years of the study. Vertically expandable prosthetic titanium ribs decreased from a peak of 48% to 6%; growth-guidance devices decreased from 10% to 3%. No change was seen in mean surgical lengthening intervals (range, 6 to 9 mo) for the 614 patients with recorded lengthenings. Final fusion was performed in 88% of patients who had undergone definitive treatment, occurring at a mean age of 13.4±2.4 years. CONCLUSIONS: From 2007 to 2017, neuromuscular EOS was the most common diagnosis for patients treated with growth-friendly implants. Patient age at first surgery and the use of magnetically controlled growing rods increased during this time. Preoperative curve magnitude, traditional growing rod lengthening intervals, and rates of final fusion did not change. LEVEL OF EVIDENCE: Level II.

Accuracy of the Spinal Pain Diagram Is Influenced by Patient Health Literacy in Completion of the Scoliosis Research Society30 Questionnaire.

The Scoliosis Research Society Questionnaire (SRS30) was designed to measure healthrelated quality of life in scoliosis patients. Patients with low health literacy may need specific guidance when providing feedback on the SRS30 so that reliable and valid results are collected for clinical decision making. The purpose of this research study was to investigate the health literacy demands of the Scoliosis Research Society Questionnaire (SRS30) and to determine if health literacy best practices mitigate errors for patients with low health literacy. Readability assessment, focus groups and structured interviews were used. Results indicated that patients with low health literacy perceived health literacy best practices as helpful in completing the SRS30 drawing. Additionally, patients with inadequate health literacy had a higher proportion of errors in pain location on the drawing (p = 0.0325) compared to patients with adequate health literacy. (Journal of Surgical Orthopaedic Advances 29(1):3942, 2020).

Inhibition of Interleukin-23-Mediated Inflammation with a Novel Small Molecule Inverse Agonist of RORγt.

Blockade of interleukin (IL)-23 or IL-17 with biologics is clinically validated as a treatment of psoriasis. However, the clinical impact of targeting other nodes within the IL-23/IL-17 pathway, especially with small molecules, is less defined. We report on a novel small molecule inverse agonist of retinoid acid-related orphan receptor (ROR) γt and its efficacy in preclinical models of psoriasis and arthritis. 1-(2,4-Dichloro-3-((1,4-dimethyl-6-(trifluoromethyl)-1H-indol-2-yl)methyl)benzoyl)piperidine-4-carboxylic acid (A-9758) was optimized from material identified from a high-throughput screening campaign. A-9758 is selective for RORγt and exhibits robust potency against IL-17A release both in vitro and in vivo. In vivo, we also show that IL-23 is sufficient to drive the accumulation of RORγt+ cells, and inhibition of RORγt significantly attenuates IL-23-driven psoriasiform dermatitis. Therapeutic treatment with A-9758 (i.e., delivered during active disease) was also effective in blocking skin and joint inflammation. Finally, A-9758 exhibited efficacy in an ex vivo human whole blood assay, suggesting small molecule inverse agonists of RORγt could be efficacious in human IL-17-related diseases. SIGNIFICANCE STATEMENT: Using a novel small molecule inverse agonist, and preclinical assays, we show that RORγt is a viable target for the inhibition of RORγt/Th17-driven diseases such as psoriasis. Preclinical models of psoriasis show that inhibition of RORγt blocks both the accumulation and effector function of IL-17-producing T cells.

Curve Modulation and Apex Migration Using Shilla Growth Guidance Rods for Early-onset Scoliosis at 5-Year Follow-up.

BACKGROUND: The Shilla procedure was designed to correct and control early-onset spinal deformity while harnessing a child's remaining spinal growth. It allows for controlled axial skeletal growth within the construct, avoiding the need for frequent surgeries to lengthen implants. We hypothesized that curve characteristics evolve over time after initial apex fusion and placement of the Shilla implants. The purpose of this study was to identify trends in curve evolution after Shilla implantation and understand how these changes influence ultimate outcome. METHODS: A single-center, retrospective review of all patients with Shilla implants in place for ≥5 years yielded 21 patients. Charts and radiographs were reviewed to compare coronal curve characteristics preoperatively, postoperatively, and at last follow-up to note changes in the apex of the primary curve. Also noted were the development of adjacent compensatory curves, the overall vertical spinal growth, and the need for definitive spinal fusion once skeletal maturity was reached. RESULTS: Of the 21 patients, the curve apex migrated caudally in 12 patients (57%) and cephalad in 1 patient (5%), with a mean migration of 2.7 vertebral levels. Two patients (10%) developed new, significant compensatory curves (1 caudal and 1 cephalad). All patients demonstrated spinal growth in T1-S1 length following index surgery (mean, 45 mm). At skeletal maturity, 10 patients underwent definitive posterior spinal fusion and instrumentation, and 3 underwent implant removal alone. CONCLUSIONS: This study constitutes the longest follow-up of Shilla patients evaluating curve and implant behavior. Results of this review suggest that the apex of the fused primary curve shifts in approximately 62% of patients, with nearly all of these (92%) involving a distal migration. Compensatory curves did develop after Shilla placement as well. Overall, these findings represent adding-on distal to the apex after Shilla instrumentation rather than a crankshaft phenomenon about the apex. A better understanding of spinal growth mechanics and outcomes after Shilla placement may improve our ability to appropriately select patients and instrumentation levels. LEVEL OF EVIDENCE: Level III.

Growth-Friendly Spine Surgery in Escobar Syndrome.

BACKGROUND: The aims of this study were to characterize the spinal deformity of patients with Escobar syndrome, describe results of growth-friendly treatments, and compare these results with those of an idiopathic early-onset scoliosis (EOS) cohort to determine whether the axial stiffness in Escobar syndrome limited correction. METHODS: We used 2 multicenter databases to review the records of 8 patients with EOS associated with Escobar syndrome who had at least 2-year follow-up after initiation of growth-friendly treatment from 1990 to 2016. An idiopathic EOS cohort of 16 patients matched for age at surgery (±1 y), postoperative follow-up (±1 y), and initial curve magnitude (±10 degrees) was identified. A randomized 1:2 matching algorithm was applied (α=0.05). RESULTS: In the Escobar group, spinal deformity involved 7 to 13 vertebrae and ranged from no vertebral anomalies in 3 patients to multiple segmentation defects in 6 patients. Mean age at first surgery was 5 years (range, 1.4 to 7.8 y) with a mean follow-up of 7.5 years (range, 4.0 to 10 y). Mean major curve improved from 76 degrees at initial presentation, to 43 degrees at first instrumentation, to 37 degrees at final follow-up (both P<0.001). Mean pelvic obliquity improved from 16 degrees (range, 5 to 31 degrees) preoperatively to 4 degrees (range, 0 to 8 degrees) at final follow-up (P=0.005). There were no differences in the mean percentage of major curve correction between the idiopathic EOS and Escobar groups at the immediate postoperative visit (P=0.743) or final follow-up (P=0.511). There were no differences between the cohorts in T1-S1 height at initial presentation (P=0.129) or in growth per month (P=0.211). CONCLUSIONS: Multiple congenital fusions and spinal curve deformity are common in Escobar syndrome. Despite large areas of congenital fusion, growth-friendly constructs facilitate spinal growth and improve curve correction. These results are comparable to those in idiopathic EOS. LEVEL OF EVIDENCE: Level III-case-control study.

ABBV-105, a selective and irreversible inhibitor of Bruton's tyrosine kinase, is efficacious in multiple preclinical models of inflammation.

OBJECTIVES: Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase required for intracellular signaling downstream of multiple immunoreceptors. We evaluated ABBV-105, a covalent BTK inhibitor, using in vitro and in vivo assays to determine potency, selectivity, and efficacy to validate the therapeutic potential of ABBV-105 in inflammatory disease. METHODS: ABBV-105 potency and selectivity were evaluated in enzymatic and cellular assays. The impact of ABBV-105 on B cell function in vivo was assessed using mechanistic models of antibody production. Efficacy of ABBV-105 in chronic inflammatory disease was evaluated in animal models of arthritis and lupus. Measurement of BTK occupancy was employed as a target engagement biomarker. RESULTS: ABBV-105 irreversibly inhibits BTK, demonstrating superior kinome selectivity and is potent in B cell receptor, Fc receptor, and TLR-9-dependent cellular assays. Oral administration resulted in rapid clearance in plasma, but maintenance of BTK splenic occupancy. ABBV-105 inhibited antibody responses to thymus-independent and thymus-dependent antigens, paw swelling and bone destruction in rat collagen induced arthritis, and reduced disease in an IFNα-accelerated lupus nephritis model. BTK occupancy in disease models correlated with in vivo efficacy. CONCLUSION: ABBV-105, a selective BTK inhibitor, demonstrates compelling efficacy in pre-clinical mechanistic models of antibody production and in models of rheumatoid arthritis and lupus.

A Comparison of SHILLA GROWTH GUIDANCE SYSTEM and Growing Rods in the Treatment of Spinal Deformity in Children Less Than 10 Years of Age.

BACKGROUND: The purpose of this study was to compare the outcomes of the SHILLA GROWTH GUIDANCE SYSTEM and "intermittent distraction growing rod" (IDGR) in the treatment of children (less than 10 y of age) with progressive spinal deformity. This was a multicenter retrospective study of the SHILLA used as an alternative treatment to IDGR to support an HDE submission for Food and Drug Administration approval. METHODS: Inclusion criteria were progressive scoliosis in a patient less than 10 years of age at index procedure. The study population consisted of 19 SHILLA and 6 IDGR patients whose mean age was 6.1 and 5.8 years, respectively. Group demographics were similar between the 2 groups. RESULTS: The initial major curve magnitude was 70.3 degrees for SHILLA and 68.3 degrees for IDGR, which decreased postoperatively to 22.4 degrees (68.1% improvement) and 32.2 degrees (52.9% improvement). During the first 4 years the correction for SHILLA varied from 40.5% to 53.4% and for IDGR from 40.9% to 56.9%. At last follow-up, T1-S1 length was 32.9 cm for SHILLA (4.2 increase from preoperation) and 34.0 cm (5.0 cm increase from preoperation) for IDGR. Average growth per month from T1-S1: SHILLA 0.14 cm, IDGR 0.11 cm. Sagittal T2-T12 preoperatively was 36.3 degrees for SHILLA and 30.0 degrees for IDGR. There were 29 reoperations in 12 of the 19 SHILLA patients (63.2%) and 40 reoperations in all 6 of the IDGR patients (100%) related to the index procedure. CONCLUSIONS: The SHILLA GROWTH GUIDANCE SYSTEM compares favorably with traditional IDGR constructs in terms of correction of the major curve, spinal length and growth, and maintenance of sagittal alignment. The >4-fold decrease in additional surgeries makes the SHILLA an attractive alternative to minimize comorbidities associated with additional surgeries. LEVELS OF EVIDENCE: Level III.

Syk Inhibition Induces Platelet Dependent Peri-islet Hemorrhage in the Rat Pancreas.

Spleen tyrosine kinase (Syk) is a nonreceptor tyrosine kinase that is an important signaling enzyme downstream of immunoreceptors containing an intracellular immunoreceptor tyrosine activating motif (ITAM). These receptors encompass a wide variety of biological functions involved in autoimmune disease pathogenesis. There has been considerable interest in the development of inhibitors of the Syk pathway for the treatment of rheumatoid arthritis and systemic lupus erythematosus. We report that Syk inhibition mechanistically caused peri-islet hemorrhages and fibrin deposition in the rat pancreas and that this finding is due to a homeostatic functional defect in platelets. In more limited studies, similar lesions could not be induced in mice, dogs, and cynomolgus monkeys at similar or higher plasma drug concentrations. Irradiation-induced thrombocytopenia caused a phenotypically similar peri-islet pancreas lesion and the formation of this lesion could be prevented by platelet transfusion. In addition, Syk inhibitor-induced lesions were prevented by the coadministration of prednisone. A relatively greater sensitivity of rat platelets to Syk inhibition was supported by functional analyses demonstrating rat-specific differences in response to convulxin, a glycoprotein VI agonist that signals through Syk. These data demonstrate that the Syk pathway is critical in platelet-endothelial cell homeostasis in the peri-islet pancreatic microvasculature in rats.

The Shilla growth guidance technique for early-onset spinal deformities at 2-year follow-up: a preliminary report.

BACKGROUND: The Shilla growth guidance technique has been developed to treat spinal deformities without the necessity of repeated operative lengthenings. The dual stainless steel rods are fixed to the corrected apex of the curve by pedicle screws with limited fusion about the apex. Vertebral growth occurs in a cephalad and caudad direction through extraperiosteally placed sliding pedicle screws. A retrospective review of patients treated with the Shilla growth guidance technique for early-onset spinal deformity was performed to study patients with >2-year follow-up and describe outcome parameters. METHODS: From a cohort of 38 patients, 10 patients with a mean age of 7 + 6 years were identified as qualifying for 2-year follow-up inclusion. RESULTS: The average preoperative curve of 70.5 degrees was corrected to 27 degrees at 6 weeks follow-up and maintained at 2-year follow-up. The space available for lung improved an average of 13%. Truncal height (C7 to S1) increased an average of 12%. One patient required rod revision, 1 required rod change to a smaller size rod, and 1 required rod replacement. Two patients required wound debridement for low-grade infection in the early-postoperative period for a total of 5 procedures beyond the index correction. No patient had changes neurologically as a result of surgery. Patients were braced for the first 3 months postoperatively while the fusion was incorporating then not thereafter. CONCLUSIONS: At 2-year follow-up, the Shilla procedure has allowed children correction of their spinal deformity with an acceptable complication rate and ability to grow brace free without repeated trips to the operating room for lengthenings. These patients would have had 49 scheduled lengthening procedures after their initial correction if treated by conventional distraction growing rod methods. LEVEL OF EVIDENCE: IV case series of therapeutic study investigating results of treatment.

Spinal height for growth guidance treatment in early onset idiopathic scoliosis: analysis through final surgical treatment.

BACKGROUND: The growth guidance (GG) method for treatment of early onset scoliosis has as its primary goal the restoration of apical spinal alignment, facilitating normal spinal growth to achieve a suitable adult thoracic height. PURPOSE: To evaluate whether GG surgical treatment achieves comparable thoracic and spinal height to distraction-based treatment (DBT) in idiopathic early onset scoliosis (I-EOS) patients. We hypothesized that GG would prove superior to DBT at the time of definitive fusion surgery. METHODS: All I-EOS patients who underwent GG at a single center were reviewed. T1-L1 and T1-S1 heights were measured using the traditional coronal method as well as the Halifax sagittal spinal length (SSL) technique. The same measurements were obtained from a comparable control group obtained from a multi-center pediatric early onset scoliosis database who underwent treatment with traditional growing rods (TGR) or magnetically controlled growing rods (MCGR). RESULTS: Of the I-EOS patients who underwent GG 2004-2019, 15 patients underwent final fusion after GG completion, with a mean 5.5 years of GG treatment prior to fusion (range 2.0-11.4 years). Mean age at GG implantation was 8.4 years (range 2.0-11.7 years); 7 were male and 8 female. GG patients experienced a mean coronal thoracic height increase of 6.2 cm during treatment through final fusion, and a mean coronal spinal height increase of 8.8 cm. At the time of final fusion, GG patients achieved greater significant mean increases than DBT patients by 2.9 cm in coronal thoracic height (p = 0.0023), 4.5 cm in coronal spinal height (p = 0.001), and 4.0 cm in SSL spinal height (p = 0.01). No GG patient concluded treatment with a thoracic height less than 18 cm in either coronal or sagittal plane. CONCLUSIONS: Not only did 100% of GG patients reach minimum thoracic height of 18 cm at time of final fusion, but GG also proved to be superior to distraction-based constructs in a comparison cohort on 3 of 4 spinal elongation measures. LEVEL OF EVIDENCE: 3.

Changes in sagittal balance and pre-existing junctional angle influence development of proximal junctional kyphosis in growth guidance systems for early-onset scoliosis.

PURPOSE: Proximal junctional kyphosis (PJK) has been reported to occur at a rate of about 30% in traditional growing rods (GR) and magnetically controlled growing rods (MCGR). Growth guidance systems (GGS) have non-rigid, gliding fixation along rods, which may mitigate PJK. There have been no studies done in shilla around PJK, hence this study aimed to assess the occurrence, risk factors, and timeline of PJK. METHODS: A prospective, multicenter database was queried for EOS patients who underwent surgery utilizing GGS. INCLUSION CRITERIA: < 10 years at index surgery and > 2 year follow-up. RESULTS: Sixty-five patients (thirty-six female) met inclusion criteria. Mean age at index surgery was 6.2 y/o (2-9); mean follow-up was 66 m. Most common etiologies were syndromic (n = 23). Mean thoracic kyphosis at pre-op was 41.8°, post-op was 35.5°, and final was 42.2°. Mean PJA at pre-op was 6.15°, post-op 1 was 4.2°, and final was 15.6°. Incidence of PJK at post-op was 35% and final was 43%. Pre-op sagittal balance and change in sagittal balance from pre-op to post-op were associated with post-op PJK (p = 0.05, 0.02). Change in spinal height from pre-op to post-op was associated with PJK at final (p = 0.04). Interestingly, increased PJA at pre-op was significantly associated with decreased PJK at post-op and final (p = 0.01, 0.03). CONCLUSION: PJK was identified in 43% of patients post-operatively after GGS for EOS. Pre-op PJA was negatively correlated with an increased incidence of PJK. Changes in sagittal balance, in either direction, was the strongest predictor for development of PJK post-operatively.

Pride Medical at Capitol Hill: A New Lesbian, Gay, Bisexual, Transgender, Queer/Questioning plus (LGBTQ+) Patient Care Option at Kaiser Permanente Mid-Atlantic States.

When accessing medical care, lesbian, gay, bisexual, transgender, queer/questioning plus (LGBTQ+) individuals face many known challenges, including stigma, discrimination, and health disparities. Transgender and nonbinary individuals often encounter physicians and staff who are not knowledgeable about gender-affirming services and the transition journey. Finding an affirming physician can be a trial-and-error process, causing concern and uncertainty. In 2021, Kaiser Permanente Mid-Atlantic States (KPMAS) researchers published a study examining the gaps in care and experience for transgender and nonbinary patients within the KPMAS healthcare system. KPMAS realized an opportunity to both close the gaps in care identified by transgender and nonbinary patients and enhance services for the broader LGBTQ+ patient community by creating Pride Medical at Capitol Hill-an additional and optional care site for individuals who identify as LGBTQ+. During the analysis timeframe of 30 June 2021 through 30 November 2022, 586 patients accessed care through 763 visits. A total of 675 visits (88%) were for primary care and 88 (12%) for OB/GYN. Over 50% (n = 384) of total visits were conducted virtually. The plurality of patients seen identified as a man (35%; n = 204) and gay (30%; n = 176). Postvisit survey results showed that 92% of survey respondents strongly agreed that the physician treated them with courtesy and respect, and 72% of survey respondents rated their overall care as excellent. Survey results show high acceptability of this program among the patients served. Pride Medical does not carve out care. The program offers patients access to a more specialized team of physicians-a similar model to other specialties-that is easily found by the division name Pride Medical. Layering additional specialty divisions on top of existing care, for interested patients, could be an option for other medical groups and health systems seeking to offer additional options of care for interested LGBTQ+ patients.

Anti-PL12 Anti-Synthetase Syndrome and Amyotrophic Lateral Sclerosis: A Case Report of a Rare Comorbidity.

BACKGROUND Anti-PL-12 syndrome is a rare form of myositis. Amyotrophic lateral sclerosis (ALS) is the commonest of the motor neuron disorders. However, the 2 conditions have not been reported to occur together in a single individual. This case report describes a patient who was diagnosed with anti-PL-12 anti-synthetase syndrome and then subsequently was diagnosed with ALS. CASE REPORT A 55-year-old male patient had anti-PL-12 syndrome and ALS occurring together. The patient initially presented with musculoskeletal complaints and was diagnosed with anti-PL-12 syndrome. He later went on to develop shortness of breath. Neurophysiological testing subsequently confirmed ALS as the patient experienced worsening muscle weakness over a 2-year period. A muscle biopsy performed showed neurogenic and myopathic process. The patient eventually lost the ability to ambulate without mobility assistance and suffered cardiac arrest due to complications from ALS, specifically diaphragmatic dysfunction. CONCLUSIONS This case report represents the first documented case of a patient having both anit-PL-12 syndrome and ALS together. It has been suggested that having an autoimmune disease (AID) may increase the subsequent risk of developing ALS. Previous studies did not conduct evaluation to ascertain serological markers for AS antibodies. Lab tests were rechecked and revalidated multiple times in separate facilities for confirmation of results in case of initial lab error. This may suggest a common etiology for both anti-PL-12 syndrome and ALS.

Myelopathic Patients Undergoing Severe Pediatric Spinal Deformity Surgery Can Improve Neurologic Function to That of Non-Myelopathic Patients by 1-Year Postoperative.

STUDY DESIGN: Multi-center, prospective, observational cohort. OBJECTIVE: To compare myelopathic vs. non-myelopathic ambulatory patients in short- and long-term neurologic function, operative treatment, and patient-reported outcomes. METHODS: Pediatric deformity patients from 16 centers were enrolled with the following inclusion criteria: aged 10-21 years-old, a Cobb angle ≥100° in either the coronal or sagittal plane or any sized deformity with a planned 3-column osteotomy, and community ambulators. Patients were dichotomized into 2 groups: myelopathic (abnormal preoperative neurologic exam with signs/symptoms of myelopathy) and non-myelopathic (no clinical signs/symptoms of myelopathy). RESULTS: Of 311 patients with an average age of 14.7 ± 2.8 years, 29 (9.3%) were myelopathic and 282 (90.7%) were non-myelopathic. There was no difference in age (P = 0.18), gender (P = 0.09), and Risser Stage (P = 0.06), while more patients in the non-myelopathic group had previous surgery (16.1% vs. 3.9%; P = 0.03). Mean lower extremity motor score (LEMS) in myelopathic patients increased significantly compared to baseline at every postoperative visit: Baseline: 40.7 ± 9.9; Immediate postop: 46.0 ± 7.1, P = 0.02; 1-year: 48.2 ± 3.7, P < 0.001; 2-year: 48.2 ± 7.7, P < 0.001). The non-myelopathic group had significantly higher LEMS immediately postoperative (P = 0.0007), but by 1-year postoperative, there was no difference in LEMS between groups (non-myelopathic: 49.3 ± 3.6, myelopathic: 48.2 ± 3.7, P = 0.10) and was maintained at 2-years postoperative (non-myelopathic: 49.2 ± 3.3, myelopathic: 48.2 ± 5.7, P = 0.09). Both groups improved significantly in all SRS domains compared to preoperative, with no difference in scores in the domains for pain (P = 0.12), self-image (P = 0.08), and satisfaction (P = 0.83) at latest follow-up. CONCLUSION: In severe spinal deformity pediatric patients presenting with preoperative myelopathy undergoing spinal reconstructive surgery, myelopathic patients can expect significant improvement in neurologic function postoperatively. At 1-year and 2-year postoperative, neurologic function was no different between groups. While non-myelopathic patients had significantly higher postoperative outcomes in SRS mental-health, function, and total-score, both groups had significantly improved outcomes in every SRS domain compared to preoperative.

Re-evaluating consensus and uncertainty among treatment options for early onset scoliosis: a 10-year update.

PURPOSE: Consensus and uncertainty in early onset scoliosis (EOS) treatment were evaluated in 2010. It is currently unknown how treatment preferences have evolved over the past decade. The purpose of this study was to re-evaluate consensus and uncertainty among treatment options for EOS patients to understand how they compare to 10 years ago. METHODS: 11 pediatric spinal surgeons (similar participants as in 2010) were invited to complete a survey of 315 idiopathic and neuromuscular EOS cases (same cases as in 2010). Treatment options included the following: conservative management, distraction-based methods, growth guidance/modulation, and arthrodesis. Consensus was defined as ≥ 70% agreement, and uncertainty was < 70%. Associations between case characteristics and consensus for treatments were assessed via chi-squared and multiple regression analyses. Case characteristics associated with uncertainty were described. RESULTS: Eleven surgeons [31.7 ± 7.8 years of experience] in the original 2010 cohort completed the survey. Consensus for conservative management was found in idiopathic patients aged ≤ 3, whereas in 2010, some of these cases were selected for surgery. There is currently consensus for casting idiopathic patients aged 1 or 2 with moderate curves, whereas in 2010, there was uncertainty between casting and bracing. Among neuromuscular cases with consensus for surgery, arthrodesis was chosen for patients aged 9 with larger curves. CONCLUSION: Presently, preferences for conservative management have increased in comparison to 2010, and casting appears to be preferred over bracing in select infantile cases. Future research efforts with higher levels-of-evidence should be devoted to elucidate the areas of uncertainty to improve care in the EOS population. LEVEL OF EVIDENCE: Level V.

Targeting the Tyrosine Kinase 2 (TYK2) Pseudokinase Domain: Discovery of the Selective TYK2 Inhibitor ABBV-712.

Tyrosine kinase 2 (TYK2) is a nonreceptor tyrosine kinase that belongs to the JAK family also comprising JAK1, JAK2, and JAK3. TYK2 is an attractive target for various autoimmune diseases as it regulates signal transduction downstream of IL-23 and IL-12 receptors. Selective TYK2 inhibition offers a differentiated clinical profile compared to currently approved JAK inhibitors. However, selectivity for TYK2 versus other JAK family members has been difficult to achieve with small molecules that inhibit the catalytically active kinase domain. Successful targeting of the TYK2 pseudokinase domain as a strategy to achieve isoform selectivity was recently exemplified with deucravacitinib. Described herein is the optimization of selective TYK2 inhibitors targeting the pseudokinase domain, resulting in the discovery of the clinical candidate ABBV-712 (21).

Perioperative Complications and Health-related Quality of Life Outcomes in Severe Pediatric Spinal Deformity.

STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To evaluate perioperative complications and mid-term outcomes for severe pediatric spinal deformity. SUMMARY OF BACKGROUND DATA: Few studies have evaluated the impact of complications on health-related quality of life (HRQoL) outcomes in severe pediatric spinal deformity. METHODS: Patients from a prospective, multicenter database with severe pediatric spinal deformity (minimum of 100 degree curve in any plane or planned vertebral column resection (VCR)) with a minimum of 2-years follow-up were evaluated (n=231). SRS-22r scores were collected preoperatively and at 2-years postoperatively. Complications were categorized as intraoperative, early postoperative (within 90-days of surgery), major, or minor. Perioperative complication rate was evaluated between patients with and without VCR. Additionally, SRS-22r scores were compared between patients with and without complications. RESULTS: Perioperative complications occurred in 135 (58%) patients, and major complications occurred in 53 (23%) patients. Patients that underwent VCR had a higher incidence of early postoperative complications than patients without VCR (28.9% vs. 16.2%, P =0.02). Complications resolved in 126/135 (93.3%) patients with a mean time to resolution of 91.63 days. Unresolved major complications included motor deficit (n=4), spinal cord deficit (n=1), nerve root deficit (n=1), compartment syndrome (n=1), and motor weakness due to recurrent intradural tumor (n=1). Patients with complications, major complications, or multiple complications had equivalent postoperative SRS-22r scores. Patients with motor deficits had lower postoperative satisfaction subscore (4.32 vs. 4.51, P =0.03), but patients with resolved motor deficits had equivalent postoperative scores in all domains. Patients with unresolved complications had lower postoperative satisfaction subscore (3.94 vs. 4.47, P =0.03) and less postoperative improvement in self-image subscore (0.64 vs. 1.42, P =0.03) as compared to patients with resolved complications. CONCLUSION: Most perioperative complications for severe pediatric spinal deformity resolve within 2-years postoperatively and do not result in adverse HRQoL outcomes. However, patients with unresolved complications have decreased HRQoL outcomes.