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BACKGROUND: Total shoulder arthroplasty is performed by orthopedic surgeons with various fellowship training backgrounds. Whether surgeons performing shoulder arthroplasty with different types of fellowship training have differing rates of complications and reoperation remains unknown. METHODS: The PearlDiver Mariner database was retrospectively queried from the years 2010-2022. Patients undergoing shoulder arthroplasty were selected using the CPT code 23472. Those undergoing revision arthroplasty and those with a history of fracture, infection, or malignancy were excluded. Fellowship was determined and verified via online search. Only surgeons who performed a minimum of 10 cases were selected; and PearlDiver was queried using their provider ID codes. Primary outcome measures included 90-day, 1-year, and 5-year rates of complication and reoperation. A Bonferroni correction was utilized in which the significance threshold was set at p≤0.00023 RESULTS: In total, 150,385 patients met the inclusion criteria and were included in the study. Analysis of surgical trends revealed that Sports Medicine and Shoulder and Elbow fellowship- trained surgeons are performing an increasing percentage of all shoulder arthroplasty over time, with each cohort exhibiting am 11.3% and 4.2% increase from 2010 to 2022, respectively. The geographic region with the highest proportion of cases performed by Sports Medicine surgeons was the West, while the Northeast has the highest proportion of cases performed by Shoulder and Elbow surgeons. Shoulder and Elbow surgeons operated on patients that were significantly younger and had fewer comorbidities. Both Shoulder and Elbow and Sports Medicine surgeons had lower rates of postoperative complications at 90 days, 1 year and 5 years in comparison to surgeons who completed another type of fellowship or no fellowship. Across each time point, the rates of individual complications between Sports Medicine and Shoulder and Elbow were comparable, but the pooled complication rate was lowest in the Shoulder and Elbow cohort. CONCLUSION: Surgeons who have completed either a Sports Medicine or Shoulder and Elbow fellowship are performing an increasing proportion of shoulder arthroplasty over time. Sports Medicine and Shoulder and Elbow-trained surgeons have significantly lower complication rates at 90 days, 1 year and 5 years postoperatively. The individual complication rates between Sports Medicine and Shoulder and Elbow are comparable, but Shoulder and Elbow has the lowest pooled complication rates overall.
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BACKGROUND: Osteoporosis is common among patients undergoing primary total hip arthroplasty (THA). This study aimed to evaluate the effect of bisphosphonate treatment on osteoporotic patients undergoing primary THA. METHODS: Using a national database, 30,137 patients who had osteoporosis before primary elective THA were identified during 2010 to 2020. Patients undergoing nonelective THA and those using corticosteroids or other medications for osteoporosis were excluded. Bisphosphonate users and bisphosphonate naïve patients were matched 1:1 based on age, sex, Elixhauser comorbidity index, and a history of obesity, rheumatoid arthritis, tobacco use, and alcohol abuse. Kaplan-Meier and multivariate analyses were used to compare 2-year outcomes between groups. RESULTS: Among matched cohorts of 9,844 patients undergoing primary THA, bisphosphonate use was associated with a significantly higher 2-year rate of periprosthetic fracture (odds ratio 1.29, 95% confidence interval 1.04 to 1.61, P = .022). There was a trend toward increased risk of any revision with bisphosphonate use (odds ratio 1.19, confidence interval 1.00 to 1.41, P = .056). Rates of infection, aseptic loosening, dislocation, and mortality were not statistically different between bisphosphonate users and bisphosphonate-naïve patients. CONCLUSION: In osteoporotic patients, bisphosphonate use before primary THA is an independent risk factor for periprosthetic fracture. Additional longer-term data are needed to determine the underlying mechanism for this association and identify preventative measures.
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Artroplastia de Quadril , Fraturas do Quadril , Osteoporose , Fraturas Periprotéticas , Humanos , Fraturas Periprotéticas/epidemiologia , Fraturas Periprotéticas/etiologia , Difosfonatos/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/cirurgia , Fatores de Risco , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Reoperação , Estudos RetrospectivosRESUMO
BACKGROUND: Lateral unicompartmental knee arthroplasty (UKA) is an effective treatment for isolated lateral compartment osteoarthritis. However, due to the rarity of the procedure, long-term outcomes and survivorship are poorly understood. We report the clinical and radiographic outcomes after lateral UKA. METHODS: We retrospectively reviewed a consecutive series of patients who underwent lateral UKA by a single fellowship-trained arthroplasty surgeon from 2001 to 2021 with a minimum 2 year follow up. There were 161 knees in 153 patients (average age 69 years) that met inclusion criteria, with a mean follow up of 10.0 years (range 0.05 to 22.2). All patients underwent the procedure via a minimally invasive lateral parapatellar approach with a fixed-bearing implant. Patient demographics, complications, radiographic findings, patient-reported outcomes, and the need for revision surgery were evaluated. Survivorship was defined with the end point as revision of components. RESULTS: There were 8 patients (5.0%) who underwent conversion to total knee arthroplasty for lateral UKA implant failure or progression of arthritis. There were 3 patients (1.9%) who underwent ipsilateral medial UKA due to medial compartment arthritis progression with preserved mechanical alignment and patellofemoral joint. There were 8 additional procedures that did not require implant changes, including 5 irrigation and debridements for acute periprosthetic joint infection (3.1%), 2 wound closures for dehiscence (1.3%), and one loose body removal (0.6%). CONCLUSIONS: Lateral UKA showed a survivorship rate of 98.0% at 5 years, 96.0% at 10 years, and 94.5% at 15 years. When including patients who underwent additional surgery for the progression of arthritis, survivorship was 97.4% at 5 years, 95.4% at 10 years, and 91.3% at 15 years. Lateral UKA should be seen as a durable treatment option for isolated lateral compartment osteoarthritis.
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BACKGROUND: Synovial fluid analysis is an essential tool in diagnosing periprosthetic joint infection (PJI) after total knee arthroplasty (TKA). However, concern exists that aspiration may introduce infection into a noninfected joint. Therefore, the purpose of this study was to evaluate the incidence of iatrogenic PJI following diagnostic knee aspiration done within 6 months of the primary TKA. METHODS: Between 2017 and 2021, the senior surgeon performed over 4,000 primary TKAs and aspirated 155 knees in 137 patients for whom there was a suspicion for PJI within 6 months of their primary TKA. There were 22 knees diagnosed as infected from the initial aspiration and therefore were excluded from the study. The remaining 133 aspirates in 115 patients who were negative for infection were followed for 6 months for signs and symptoms of PJI to elucidate whether aspiration introduced infection into an initially noninfected joint. RESULTS: There were 70 of 133 knees (52.6%) aspirated between 0 and 6 weeks after index TKA, 40 of 133 (30.1%) between 6 weeks and 3 months, and 23 of 133 (17.3%) between 3 and 6 months. At final follow-up, none of the 133 initially noninfected knees exhibited evidence of subsequent iatrogenic PJI or had subsequent surgery for infection. CONCLUSION: While joint aspiration is a procedure with inherent risks, this study shows that the rate of iatrogenic PJI is extremely low (0%). Therefore, if infection is suspected, the surgeon should consider joint aspiration, even in the initial postoperative period, as the risk for introducing infection is far outweighed by the risk of missing an infection.
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Artrite Infecciosa , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/diagnóstico , Artroplastia do Joelho/efeitos adversos , Risco , Articulação do Joelho/cirurgia , Artrite Infecciosa/etiologia , Doença Iatrogênica/epidemiologia , Estudos RetrospectivosRESUMO
PURPOSE: To compare the different interventions described in the literature for the surgical treatment of small and medium complete rotator cuff tears. METHODS: A systematic review of randomized controlled trials of small-medium, full-thickness rotator cuff tears published since 2000 was performed. Clinical characteristics, re-tear rates, range of motion (ROM), and patient-reported outcomes (PRO) data were collected. Interventions were compared via arm-based Bayesian network meta-analysis in a random-effects model. Interventions were ranked for each domain (re-tear risk, pain, ROM, and PROs) via surface under the cumulative ranking curves. RESULTS: A total of 18 studies comprising 2046 shoulders (47% females, mean age 61 ± 3 years, mean follow-up 21 ± 5 months) were included. Interventions that ranked highest for minimizing re-tear risk included arthroscopic single-row repair (A+SR) or double-row repair (A+DR) with or without platelet-rich plasma (PRP). Open repair and A+SR repair with acromioplasty (ACP) ranked highest for pain relief. Interventions that ranked highest for ROM improvement included open repair, PT, and A+DR with or without ACP. Interventions that ranked highest for PROs included arthroscopic footprint microfracture with or without SR, open repair, and A+SR with or without ACP. CONCLUSIONS: Based on a network meta-analysis of level 1 studies, arthroscopic rotator cuff repair with a SR or DR construct demonstrates similar retear rates, PROs, and clinical outcomes. The highest-ranking treatment for minimizing retears was arthroscopic repair with DR constructs and PRP augmentation, although open repair and arthroscopic SR remain reliable options with excellent clinical outcomes. Addition of PRP to DR constructs trended toward a 56% decreased risk of retear as compared to DR repair alone. Although no single treatment emerged superior, several interventions offered excellent clinical improvements in pain, ROM, and PROs that exceeded minimal clinically important difference thresholds. LEVEL OF EVIDENCE: I, systematic review and meta-analysis of level I studies.
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Plasma Rico em Plaquetas , Lesões do Manguito Rotador , Artroscopia , Teorema de Bayes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Ruptura , Resultado do TratamentoRESUMO
BACKGROUND: Electric scooters (e-scooters) have become a widespread method of transportation. The purpose of this study is to provide risk stratification tools for modifiable risk factors associated with e-scooter injury morbidity. METHODS: Patients at an urban Level 1 Trauma center sustaining e-scooter injuries between November 2017 through March 2020 were identified. Primary outcomes of interest were major trauma, as defined by an Injury Severity Score (ISS) >15, or hospital admission. RESULTS: A total of 442 patients sustained orthopaedic (51%), facial (31%), cranial (13%), and chest/abdominal injuries (4.5%). Rate of helmet use was 2.5%, hospital admission was 40.7%, and intensive care was 3%. Patients with facial injuries were half as likely to sustain major trauma as compared to orthopaedic injuries (p < 0.05). Factors with higher likelihood of hospital admission included age > 40 years (OR 4.20, p < 0.01), alcohol or other substance intoxication (OR 4.14 and 9.87, p < 0.001), loss of consciousness (OR 2.72, p < 0.003), or transport to the hospital by ambulance (OR 4.47, p < 0.001). CONCLUSIONS: There is a substantial proportion of major trauma within e-scooter injuries. Modifiable risk factors for hospital admission include use of head protection and substance use while riding e-scooters.
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Acidentes de Trânsito , Serviço Hospitalar de Emergência/estatística & dados numéricos , Veículos Automotores , Ferimentos e Lesões/terapia , Adulto , Consumo de Bebidas Alcoólicas , Estudos Transversais , Feminino , Dispositivos de Proteção da Cabeça , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Centros de TraumatologiaRESUMO
BACKGROUND: Stress from overhead throwing results in morphologic changes to the shoulder in youth baseball players. With greater valgus torque stresses, the elbow experiences injuries specifically attributed to throwing. However, no previous work that we know of has assessed throwing-related morphologic changes of the elbow without associated conditions. QUESTIONS/PURPOSES: (1) Do children who play competitive baseball have enlargement or overgrowth of their radial head shape and/or capitellum compared with the nondominant elbow on MRI? (2) Do children who stop playing year-round baseball have less enlargement of the lateral elbow structures than children who maintain a high level of play? METHODS: A prospective study was conducted between 2015 and 2018 on preadolescent boys who underwent voluntary MRI of their bilateral elbows before the start of the spring baseball season. Twenty-six children agreed to participate out of a four-team league that was asked to participate; their first MRI was obtained at a mean (range) age of 12 years (10 to 13). We also obtained their history related to throwing and performed a physical examination. Players had a mean of 5.6 years of playing before their first MRI, and half the children (13 of 26) were year-round baseball players. Sixty-two percent (16 of 26) reported being either or both a pitcher or catcher as their primary position. No child was excluded from participation. Three years later, these boys were asked to return for repeat MRI and physical examinations. Fifty-eight percent (15 of 26) of players were still playing at the 3-year MRI. Continued play or new onset of pain was documented. Radiographic measurements were then compared between dominant and nondominant arms, and the differences of these changes were compared between those who had continued playing during the study period and those who had quit. The measurements were made in all three planes of the radial head and capitellum, both osseous and cartilaginous. Measurement intrarater and interrater reliability were in the good-to-excellent range (intraclass correlation coefficient 0.77 to 0.98). RESULTS: When we compared dominant and nondominant arms, we found there was no dominant arm overgrowth (difference between baseline and 3-year measurements) in any measurement; for example, sagittal capitellum measurements in dominant arms were 2.5 ± 1.1 mm versus non-dominant arms: 2.8 ± 1.1 mm (mean difference -0.23 [95% CI -0.55 to 0.08]; p = 0.13). There was only undergrowth of the cartilaginous axial diameter of the radial head (change in dominant: 2.5 ± 1.3 mm; change in nondominant: 3.2 ± 1.7 mm; mean difference -0.64 mm [95% CI -1.2 to -0.06]; p = 0.03). There was no enlargement of the lateral elbow structures when children who continued to play were compared with children who stopped playing; for example, the difference in the bone-only growth ratio of the sagittal radial head to humerus of those still playing was 0.001 ± 0.03 and it was 0.01 ± 0.03 for those not playing (mean difference -0.01 [95% CI -0.04 to 0.01]; p = 0.29). CONCLUSION: In healthy children who play baseball for multiple years between the ages of 6 to 11 years, continued torque at the elbow from throwing does not result in morphologic changes as it does in the shoulder. Despite evidence that injuries and surgery because of long-term participation in a throwing sport results in a larger radial head and capitellum, our study presents evidence that outside an injured elbow, throwing alone does not appear to change the morphology of the lateral elbow. Therefore, changes to the radial head size could presuppose other elbow pathology and future study could be performed to better evaluate the correlation. LEVEL OF EVIDENCE: Level I, prognostic study.
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Beisebol/fisiologia , Cotovelo/crescimento & desenvolvimento , Imageamento por Ressonância Magnética , Adolescente , Criança , Cotovelo/diagnóstico por imagem , Humanos , Úmero/crescimento & desenvolvimento , Masculino , Exame Físico , Estudos Prospectivos , Rádio (Anatomia)/crescimento & desenvolvimentoRESUMO
Background: Proximal humerus fractures are a common injury, predominantly affecting older adults. This study aimed to develop risk-prediction models for prolonged length of hospital stay (LOS), serious adverse complications, and readmission within 30 days of surgically treated proximal humerus fractures using machine learning (ML) techniques. Methods: Adult patients (age >18) who underwent open reduction internal fixation (ORIF), hemiarthroplasty, or total shoulder arthroplasty for proximal humerus fracture between 2016 and 2021 were included. Preoperative demographic and clinical variables were collected for all patients and used to establish ML-based algorithms. The model with optimal performance was selected according to area under the curve (AUC) on the receiver operating curve (ROC) curve and overall accuracy, and the specific predictive features most important to model derivation were identified. Results: A total of 7473 patients were included (72.1% male, mean age 66.2 ± 13.7 years). Models produced via gradient boosting performed best for predicting prolonged LOS and complications. The model predicting prolonged LOS demonstrated good discrimination and performance, as indicated by (Mean: 0.700, SE: 0.017), recall (Mean: 0.551, SE: 0.017), accuracy (Mean: 0.717, SE: 0.010), F1-score (Mean: 0.616, SE: 0.014), AUC (Mean: 0.779, SE: 0.010), and Brier score (Mean: 0.283, SE: 0.010) Preoperative hematocrit, preoperative platelet count, and patient age were considered the strongest predictive features. The model predicting serious adverse complications exhibited comparable discrimination [precision (Mean: 0.226, SE: 0.024), recall (Mean: 0.697, SE: 0.048), accuracy (Mean: 0.811, SE: 0.010), F1-score (Mean: 0.341, SE: 0.031)] and superior performance relative to the LOS model [AUC (Mean: 0.806, SE: 0.024), Brier score (Mean: 0.189, SE: 0.010), noting preoperative hematocrit, operative time, and patient age to be most influential. However, the 30-day readmission model achieved the weakest relative performance, displaying low measures of precision (Mean: 0.070, SE: 0.012) and recall (Mean: 0.389, SE: 0.053), despite good accuracy (Mean: 0.791, SE: 0.009). Conclusion: Predictive models constructed using ML techniques demonstrated favorable discrimination and satisfactory-to-excellent performance in forecasting prolonged LOS and serious adverse complications occurring within 30 days of surgical intervention for proximal humerus fracture. Modifiable preoperative factors such as hematocrit and platelet count were identified as significant predictive features, suggesting that clinicians could address these factors during preoperative patient optimization to enhance outcomes. Overall, these findings highlight the potential for ML techniques to enhance preoperative management, facilitate shared decision-making, and enable more effective and personalized orthopedic care by exploring alternative approaches to risk stratification.
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Background: In 2020, the American Society of Shoulder and Elbow Therapists (ASSET) published an evidence-based consensus statement outlining postoperative rehabilitation guidelines following anatomic total shoulder arthroplasty (TSA). Purpose: The purpose of this study was to (1) quantify the variability in online anatomic TSA rehabilitation protocols, and (2) assess their congruence with the ASSET consensus guidelines. Methods: This study was a cross-sectional investigation of publicly available, online rehabilitation protocols for anatomic TSA. A web-based search was conducted in April 2022 of publicly available rehabilitation protocols for TSA. Each collected protocol was independently reviewed by two authors to identify recommendations regarding immobilization, initiation, and progression of passive (PROM) and active range of motion (AROM), as well as the initiation and progression of strengthening and post-operative exercises and activities. The time to initiation of various components of rehabilitation was recorded as the time at which the activity or motion threshold was permitted by the protocol. Comparisons between ASSET start dates and mean start dates from included protocols were performed. Results: Of the 191 academic institutions included, 46 (24.08%) had publicly available protocols online, and a total of 91 unique protocols were included in the final analysis. There were large variations seen among included protocols for the duration and type of immobilization post-operatively, as well as for the initiation of early stretching, PROM, AROM, resistance exercises, and return to sport. Of the 37 recommendations reported by both the ASSET and included protocols, 31 (83.78%) were found to be significantly different between groups (p\<0.05). Conclusion: Considerable variability was found among online post-operative protocols for TSA with substantial deviation from the ASSET guidelines. These findings highlight the lack of standardization in rehabilitation protocols following anatomic TSA. Level of Evidence: 3b.
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Background: Patients use the Internet to learn information about injuries, yet online content remains largely unstudied. This study analyzed patient questions posed online regarding ulnar collateral ligament (UCL) tears or UCL surgical management. Methods: Three separate search strings about UCL tear and UCL surgery were queried on the Google search engine. The 300 most commonly asked questions were compiled for each topic and associated webpage information was collected from the "People also ask" section. Questions were categorized using the Rothwell classification and webpages by Journal of the American Medical Association (JAMA) benchmark criteria. Results: The most frequent UCL tear questions were "how long does it take to heal a torn UCL?" and "what is nonsurgical treatment for the UCL?" The most frequent UCL surgery question was "can you retear your UCL after surgery?" The Rothwell classification of questions for UCL tear/UCL surgery was 55%/32% policy, 38%/57% fact, and 7%/11% value with highest subcategories being indications/management (46%/25%) and technical details (24%/25%). The most common webpages were academic (39%/29%) and medical practice (24%/26%). Mean JAMA score for all 600 webpages was low (1.2), with journals (mean = 3.4) having the highest score. Medical practice (mean = 0.5) and legal websites (mean = 0.0) had the lowest JAMA scores. Only 30% of webpages provided UCL-specific information. Conclusion: Online UCL patient questions commonly pertain to technical details and injury management. Webpages suggested by search engines contain information specific to UCL tears and surgery only one-third of the time. The quality of most webpages provided to patients is poor, with minimal source transparency.
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BACKGROUND: Electric scooters (e-scooters) have become a widespread method of transportation due to convenience and affordability. However, the financial impact of medical care for sustained injuries is currently unknown. The purpose of this study is to characterize total billing charges associated with medical care of e-scooter injuries. METHODS: A retrospective review of patients with e-scooter injuries presenting to the trauma bay, emergency department or outpatient clinics at an urban level 1 trauma center was conducted from November 2017 to March 2020. Demographic and clinical data were collected. Primary outcomes of interest were total billing charges and billing to insurance (hospital and professional). Multivariable models were used to identify preventable risk factors associated with higher total billing charges. RESULTS: A total of 63 patients were identified consisting of 42 (66.7%) males, average age 40.19 (SD 13.29) years and 3.2% rate of helmet use. Patients sustained orthopedic (29%, n=18), facial (48%, n=30) and cranial (23%, n=15) injuries. The average total billing charges for e-scooter clinical encounters was $95 710 (SD $138 215). Average billing to insurance was $86 376 (SD $125 438) for hospital charges and $9 334 (SD $14 711) for professional charges. There were no significant differences in charges between injury categories. On multivariable regression, modifiable risk factors independently associated with higher total billing charges included any intoxication prior to injury ($231 377 increase, p=0.02), intracranial bleeds ($75 528, p=0.04) and TBI ($360 898, p=0.006). DISCUSSION: Many patients sustain high-energy injuries during e-scooter accidents with significant medical and financial consequences. Further studies may continue expanding the financial impact of e-scooter injuries on both patients and the healthcare system. LEVEL OF EVIDENCE: III.
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OBJECTIVES: This study highlights demographics and orthopaedic injuries of electric scooter-related trauma that presented to our institution over a 27-month period. DESIGN: Retrospective review. SETTING: Urban Level 1 trauma center. PATIENTS: Patients presenting to the emergency department, trauma bay, or outpatient clinic after electric scooter injury were identified from November 2017 through January 2020 using ICD-10 diagnosis codes. MAIN OUTCOMES: Patient charts were reviewed for demographics, injury characteristics, imaging, treatment, perioperative data, and Injury Severity Scores. RESULTS: Four hundred eighty-five patients presented during the study period. Of these, 44% had orthopaedic injuries, including 30% with pelvis or extremity fractures. There were 21 (10%) polytraumatized patients in the orthopaedic cohort. The age ranged from 16 to 79 years (average 36 years), with 58% men, and 18% were visitors from out of town. Of 49 patients requiring orthopaedic surgery, 8 underwent surgery on an urgent basis. The average Injury Severity Score for orthopaedic patients was 8.4 with a median of 5.0 for nonoperative injuries versus a significantly higher median of 16.0 for operative injuries. Twenty-nine percent of patients were intoxicated and only 2% wore a helmet. CONCLUSIONS: Electric scooter injuries are increasing, and many patients sustain high-energy injuries. As electric scooter use continues to increase, the prevalence of orthopaedic injuries is also likely to rise. Further studies are needed to fully understand the impact scooter-related injuries have on individual patients and the health care system. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Ortopedia , Centros de Traumatologia , Adolescente , Adulto , Idoso , Feminino , Dispositivos de Proteção da Cabeça , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
B cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B cells exist in the cerebrospinal fluid (CSF), meninges, and CNS parenchyma of MS patients. We sought to investigate the presence of clonally related B cells over time by performing Ig heavy chain variable region repertoire sequencing on B cells from longitudinally collected blood and CSF samples of MS patients (n = 10). All patients were untreated at the time of the initial sampling; the majority (n = 7) were treated with immune-modulating therapies 1.2 (±0.3 SD) years later during the second sampling. We found clonal persistence of B cells in the CSF of 5 patients; these B cells were frequently Ig class-switched and CD27+. Specific blood B cell subsets appear to provide input into CNS repertoires over time. We demonstrate complex patterns of clonal B cell persistence in CSF and blood, even in patients on immune-modulating therapy. Our findings support the concept that peripheral B cell activation and CNS-compartmentalized immune mechanisms can in part be therapy resistant.