RESUMEN
Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.
RESUMEN
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).
Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Neutralizantes/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Vacunas de Subunidad/inmunología , Compuestos de Alumbre , Animales , Anticuerpos Antivirales/inmunología , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , COVID-19/virología , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Modelos Animales de Enfermedad , Inmunidad Celular , Inmunidad Humoral , Macaca mulatta/inmunología , Masculino , Oligodesoxirribonucleótidos , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , EscualenoRESUMEN
CCR5-tropic simian/human immunodeficiency viruses (SHIV) with clade C transmitted/founder envelopes represent a critical tool for the investigation of HIV experimental vaccines and microbicides in nonhuman primates, although many such isolates lead to spontaneous viral control post infection. Here, we generated a high-titer stock of pathogenic SHIV-C109p5 by serial passage in two rhesus macaques (RM) and tested its virulence in aged monkeys. The co-receptor usage was confirmed before infecting five geriatric rhesus macaques (four female and one male). Plasma viral loads were monitored by reverse transcriptase-quantitative PCR (RT-qPCR), cytokines by multiplex analysis, and biomarkers of gastrointestinal damage by enzyme-linked immunosorbent assay. Antibodies and cell-mediated responses were also measured. Viral dissemination into tissues was determined by RNAscope. Intravenous SHIV-C109p5 infection of aged RMs leads to high plasma viremia and rapid disease progression; rapid decrease in CD4+ T cells, CD4+CD8+ T cells, and plasmacytoid dendritic cells; and wasting necessitating euthanasia between 3 and 12 weeks post infection. Virus-specific cellular immune responses were detected only in the two monkeys that survived 4 weeks post infection. These were Gag-specific TNFα+CD8+, MIP1ß+CD4+, Env-specific IFN-γ+CD4+, and CD107a+ T cell responses. Four out of five monkeys had elevated intestinal fatty acid binding protein levels at the viral peak, while regenerating islet-derived protein 3α showed marked increases at later time points in the three animals surviving the longest, suggesting gut antimicrobial peptide production in response to microbial translocation post infection. Plasma levels of monocyte chemoattractant protein-1, interleukin-15, and interleukin-12/23 were also elevated. Viral replication in gut and secondary lymphoid tissues was extensive.IMPORTANCESimian/human immunodeficiency viruses (SHIV) are important reagents to study prevention of virus acquisition in nonhuman primate models of HIV infection, especially those representing transmitted/founder (T/F) viruses. However, many R5-tropic SHIV have limited fitness in vivo leading to many monkeys spontaneously controlling the virus post acute infection. Here, we report the generation of a pathogenic SHIV clade C T/F stock by in vivo passage leading to sustained viral load set points, a necessity to study pathogenicity. Unexpectedly, administration of this SHIV to elderly rhesus macaques led to extensive viral replication and fast disease progression, despite maintenance of a strict R5 tropism. Such age-dependent rapid disease progression had previously been reported for simian immunodeficiency virus but not for R5-tropic SHIV infections.
Asunto(s)
Infecciones por VIH , VIH , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Replicación Viral , Animales , Femenino , Masculino , Proteínas Adaptadoras Transductoras de Señales/inmunología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Envejecimiento , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Quimiocina CCL2/inmunología , Quimiocina CCL2/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/patología , Progresión de la Enfermedad , VIH/clasificación , VIH/crecimiento & desarrollo , VIH/patogenicidad , VIH/fisiología , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Infecciones por VIH/virología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucinas/inmunología , Interleucinas/metabolismo , Intestinos/virología , Tejido Linfoide/virología , Macaca mulatta/inmunología , Macaca mulatta/metabolismo , Pase Seriado , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/crecimiento & desarrollo , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Virus de la Inmunodeficiencia de los Simios/fisiología , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Carga Viral , Tropismo Viral , Virulencia , Receptores CCR5/metabolismoRESUMEN
INTRODUCTION: Growing rods (GRs) are used to treat early-onset scoliosis (EOS) recalcitrant to bracing and casting. Proximal anchor pullout, a known complication of GR constructs, can result in spinal cord injury if pedicle screw anchors are placed with a lateral-to-medial trajectory. To mitigate this risk, a more straightforward and potentially safer trajectory may result in screws that terminate within the costovertebral joint (CVJ). We asked, how often does CVJ placement occur and does this technique increase the rate of failure in GR constructs? METHODS: We retrospectively reviewed 35 patients with EOS treated with dual GR with >2-year follow-up excluding patients with skeletal dysplasia or history of previous posterior instrumentation. Patient demographics, radiographic parameters, and implant constructs were assessed. RESULTS: Of patients meeting the inclusion criteria, 18/35 (51%) were females with an average age of 7.96 (range: 4.0 to 15.2) years at surgery with a follow-up of 3.7 (range: 2.0 to 7.7) years. Five (14%) patients had idiopathic EOS, 5 (14%) had congenital EOS, 12 (34%) had neuromuscular EOS, 10 (29%) had syndromic scoliosis, and 3 (9%) had another etiology for EOS. Among 195 proximal pedicle screws placed, 19 (10%) terminated within the CVJ, and 13 patients (37%) had at least 1 CVJ screw. Two patients (6%) experienced unilateral proximal pullout. In both patients, the anchors on the affected side included 1 of 2 screws within the CVJ. Both patients had constructs that included 2 screws on the side that pulled out and 3 screws on the side that did not. None of the remaining 17 CVJ screws led to implant failure. CONCLUSION: Pedicle screw placement within the CVJ is common and does not appear to significantly contribute to proximal screw pullout; however, it may contribute to unilateral implant failure in constructs employing only 2 proximal screws, where 1 of those 2 screws terminates within the CVJ. Construct modifications should be considered in this scenario. LEVEL OF EVIDENCE: Level III.
Asunto(s)
Tornillos Pediculares , Escoliosis , Fusión Vertebral , Femenino , Humanos , Niño , Masculino , Tornillos Pediculares/efectos adversos , Escoliosis/diagnóstico por imagen , Escoliosis/cirugía , Escoliosis/etiología , Estudios Retrospectivos , Fusión Vertebral/métodos , ArticulacionesRESUMEN
BACKGROUND: Socioeconomic status (SES), race, and insurance type correlate with initial curve severity for patients with idiopathic scoliosis, but less is known regarding how these variables impact surgical outcomes. The objectives of this study were to determine the influence of SES, race, and insurance on preoperative appointment attendance, likelihood of obtaining a preoperative second opinion, brace prescription, missed 6 or 12-month postsurgical appointments, incidence of emergency department visits 0 to 90 days after surgery, and major complications within a year of surgery. METHODS: A review of 421 patients diagnosed with idiopathic scoliosis who underwent surgery at a single high-volume pediatric spinal deformity institution between May 2015 and October 2021 was conducted. Area Deprivation Index, a quantitative measure of SES, was collected. Scores were stratified by quartile; higher scores indicated a lower SES. χ 2 tests for correlation were performed to determine whether clinical outcomes were dependent upon Area Deprivation Index, race, or insurance type; P ≤0.05 was significant. RESULTS: The sample was 313 Caucasian (74%), 69 (16%) black, and 39 (9.3%) other patients.â¯More patients had private versus public insurance (80% vs 20%) and were of higher SES. The likelihood of missing preoperative appointments was higher for black patients ( P = 0.037). Those with lower SES missed more postoperative appointments and received less bracing and second opinions ( P = 0.038, P = 0.017, P = 0.008, respectively). Being black and publicly insured correlated with fewer brace prescriptions ( P < 0.001, P = 0.050) and decreased rates of obtaining second opinions ( P = 0.004,⯠P = 0.001). CONCLUSION: Patients with idiopathic scoliosis surgery who were Caucasian, privately insured, and of higher SES were more likely to seek preoperative second opinions, be prescribed a brace, and attend postoperative appointments. Recognition of the inherent health care disparities prevalent within each pediatric spine surgery referral region is imperative to better inform local and national institutional level programs to educate and assist patients and families most at risk for disparate access to scoliosis care. LEVEL OF EVIDENCE: Level III; retrospective case-control study.
Asunto(s)
Seguro , Escoliosis , Niño , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , Escoliosis/cirugía , Factores SocioeconómicosRESUMEN
BACKGROUND: Hip surveillance in cerebral palsy (CP) is an accepted practice with evidence-based guidelines implemented. For the skeletally immature with open triradiate cartilage (TRC), recommendations for radiographic surveillance stemmed from population-based studies. For nonambulatory CP, progression of hip displacement after skeletal maturity has been reported; less is known for ambulatory CP. We aimed to determine the prevalence and risk factors associated with progressive hip displacement after TRC closure, a proxy for skeletal maturity, for ambulatory CP. METHODS: This is a retrospective cohort study of patients with ambulatory CP (Gross Motor Function Classification System I-III), with unilateral or bilateral involvement, hypertonic motor type, regular hip surveillance (≥3 radiographs after age 10 yr, 1 before TRC closure, ≥1 after age 16 yr), and 2-year follow-up post-TRC closure. The primary outcome was migration percentage (MP). Other variables included previous preventative/reconstructive surgery, topographic pattern, sex, scoliosis, epilepsy, and ventriculoperitoneal shunt. An "unsuccessful hip" was defined by MP ≥30%, MP progression ≥10%, and/or requiring reconstructive surgery after TRC closure. Statistical analyses included chi-square and multivariate Cox regression. Kaplan-Meier survivorship curves were also determined. Receiver operating characteristic analysis was used to determine the MP threshold for progression to an "unsuccessful hip" after TRC closure. RESULTS: Seventy-six patients (39.5% female) met the inclusion criteria, mean follow-up 4.7±2.1 years after TRC closure. Sixteen (21.1%) patients had an unsuccessful hip outcome. By chi-square analysis, diplegia (P=0.002) and epilepsy (P=0.04) were risk factors for an unsuccessful hip. By multivariate analysis, only first MP after TRC closure (P<0.001) was a significant risk factor for progression to an unsuccessful hip; MP ≥28% being the determined threshold (receiver operating characteristic curve analysis, area under curve: 0.845, P<0.02). CONCLUSIONS: The risk of MP progression after skeletal maturity is relatively high (21%), similar to nonambulatory CP. Annual hip surveillance radiographs after TRC closure should continue for Gross Motor Function Classification System I-III with an MP ≥28% after TRC closure, especially for bilateral CP and epilepsy. LEVEL OF EVIDENCE: III.
RESUMEN
Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.
Asunto(s)
Colon/virología , Anticuerpos Anti-VIH , Infecciones por VIH , Inmunoglobulina A Secretora , Membrana Mucosa/virología , Animales , Macaca mulatta , Membrana Mucosa/inmunología , Tomografía Computarizada por Tomografía de Emisión de Positrones , RectoRESUMEN
Vertical transmission of human immunodeficiency virus (HIV) can occur in utero, during delivery, and through breastfeeding. We utilized Positron Emission Tomography (PET) imaging coupled with fluorescent microscopy of 64Cu-labeled photoactivatable-GFP-HIV (PA-GFP-BaL) to determine how HIV virions distribute and localize in neonatal rhesus macaques two and four hours after oral viral challenge. Our results show that by four hours after oral viral exposure, HIV virions localize to and penetrate the rectal mucosa. We also used a dual viral challenge with a non-replicative viral vector and a replication competent SHIV-1157ipd3N4 to examine viral transduction and dissemination at 96 hours. Our data show that while SHIV-1157ipd3N4 infection can be found in the oral cavity and upper gastrointestinal (GI) tract, the small and large intestine contained the largest number of infected cells. Moreover, we found that T cells were the biggest population of infected immune cells. Thus, thanks to these novel technologies, we are able to visualize and delineate of viral distribution and infection throughout the entire neonatal GI tract during acute viral infection.
Asunto(s)
Tracto Gastrointestinal/virología , Infecciones por VIH/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Linfocitos T/virología , Carga Viral , Animales , Animales Recién Nacidos , Radioisótopos de Cobre/análisis , VIH-1/aislamiento & purificación , Humanos , Macaca mulatta , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
AIM: To report survival probability of a large cohort of children with cerebral palsy (CP) after spinal fusion. METHOD: All children with CP who had spinal fusion between 1988 and 2018 at the reporting facility were reviewed for survival. Death records of the institutional CP database, institutional electronic medical records, publicly available obituaries, and the National Death Index through the US Centers for Disease Control were searched. Survival probabilities with different surgical eras, comorbidities, ages, and curve severities were compared using Kaplan-Meier curves. RESULTS: A total of 787 children (402 females, 385 males) had spinal fusion at a mean age of 14 years 1 month (standard deviation 3 years 2 months). The 30-year estimated survival was approximately 30%. Survival decreased for children who had spinal fusion at younger ages, longer postoperative hospital stays, longer postoperative intensive care unit stays, gastrostomy tubes, and pulmonary comorbidities. INTERPRETATION: Children with CP who required spinal fusions had reduced long-term survival compared with an age-matched typically developing cohort; however, a substantial number survived 20 to 30 years after the surgery. This study had no comparison group of children with CP scoliosis; therefore, we do not know whether correction of scoliosis affected their survival.
Asunto(s)
Parálisis Cerebral , Escoliosis , Fusión Vertebral , Masculino , Femenino , Humanos , Niño , Adolescente , Estudios de Seguimiento , Estudios Retrospectivos , Parálisis Cerebral/cirugía , Escoliosis/cirugía , Resultado del Tratamiento , ParálisisRESUMEN
AIM: To evaluate the effects of intrathecal baclofen pump (ITBP) therapy on hip dysplasia in young patients with cerebral palsy (CP). METHOD: This was a retrospective cohort series of prospectively collected data. Inclusion criteria were all patients with CP in Gross Motor Function Classification System (GMFCS) levels IV or V who underwent ITBP placement under 8 years old with at least 5 years of follow-up. Thirty-four patients were matched to a control group of 71 patients based on GMFCS level, motor type, medical comorbidities, worst hip migration percentage at ITBP placement, age, and Modified Ashworth scale scores. Patients were followed for at least 5 years or until they had hip reconstructive surgery. The primary outcome was the development of hip displacement as measured by the migration percentage at the latest follow-up or the preoperative migration percentage before hip reconstruction. RESULTS: The migration percentage at last follow-up was not statistically different between groups (ITBP: 36.2%, non-ITBP: 44.4%, p = 0.14). The rates of future preventative, reconstructive, and recurrent hip surgery were not different between groups. INTERPRETATION: The use of ITBP as an early treatment of spasticity did not alter the natural history of progressive hip displacement in non-ambulatory patients with CP and hip displacement is likely multifactorial, not solely due to spasticity.
Asunto(s)
Parálisis Cerebral , Luxación de la Cadera , Humanos , Niño , Parálisis Cerebral/complicaciones , Parálisis Cerebral/tratamiento farmacológico , Parálisis Cerebral/cirugía , Baclofeno/uso terapéutico , Luxación de la Cadera/complicaciones , Luxación de la Cadera/tratamiento farmacológico , Estudios Retrospectivos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiologíaRESUMEN
BACKGROUND: Minimally displaced fractures of the lateral humeral condyle (LHC) may be treated nonoperatively in a long arm cast, but there is not a standardized evidence-based protocol. The aim of this study was to evaluate our nonoperatively treated LHC fractures, determine the risk of subsequent displacement, analyze our practice variability, and develop an evidence-based protocol to safely manage children with LHC fractures and to evaluate potential savings related to this analysis. METHODS: We retrospectively reviewed clinical and radiographic parameters of all patients with LHC fractures at our institution from 2009 to 2015. All patients treated nonoperatively initially were included. We recorded demographic data and calculated the number of visits, casts applied, and radiographs within the first 4 weeks. We also analyzed practice variation among 27 treating providers. The number of children with subsequent displacement needing operative fixation was determined. We also looked at the average duration for each follow-up visit and the charges/costs associated with casting and radiographs. RESULTS: There were 271 children with LHC fractures treated nonoperatively. Twenty-one were excluded because of the lack of adequate radiographs. There were 157 boys and 93 girls (average age 6.7 y). According to the Jakob classification, fracture types were as follows: 1 (230), 2 (20), and 3 (0). Within the first 4 weeks, the average number of visits was 2.6 (range: 1 to 5), average number of casts was 2.4 (range: 1 to 4), and the average number of radiographs was 9.4 (range: 2 to 31). Only 3 patients with LHC fracture type Jakob 1 were taken to the operating room post injury (9, 12, and 15 d, respectively) for subsequent displacement. CONCLUSION: Displacement in appropriately selected LHC fractures treated nonoperatively was rare (3/250, 1.2%) in this cohort, and the data question the need for multiple visits and radiographs in the first 4 weeks. Optimal follow-up (proposed follow-up at 10 to 15 d after injury and then 4 to 6 wk with radiographs, including an internal oblique view) would be safe, minimize waste, and result in better value-based care. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Articulación del Codo , Fracturas Humerales Distales , Fracturas del Húmero , Artropatías , Niño , Masculino , Femenino , Humanos , Estudios Retrospectivos , Fracturas del Húmero/diagnóstico por imagen , Fracturas del Húmero/terapia , Fracturas del Húmero/complicaciones , Articulación del Codo/cirugía , Húmero , Fijación Interna de Fracturas/métodosRESUMEN
BACKGROUND: Maintaining femoral head shape (FHS) and acetabular sphericity are important goals in preventing long-term osteoarthritis in hips in children with cerebral palsy (CP). As acetabular morphology has been widely studied, our objective was to determine FHS in CP after triradiate cartilage (TRC) closure, a proxy for skeletal maturity, and the risk factors associated with residual deformity and osteoarthritis. METHODS: In this retrospective cohort study, patients with CP [Gross Motor Function Classification System (GMFCS) IV to V], minimum 4 yearly hip radiographs after age 10 years, and at least 1 radiograph after age 16 years, were included. Primary outcome was FHS (Rutz), stratified as "less severe" (Rutz A to B) and "more severe" (Rutz C to D). Secondary outcomes included migration percentage (MP), age at TRC closure, previous reconstructive (femoral with/without pelvic osteotomies) surgery, previous intrathecal baclofen, Tönnis osteoarthritis grade, and GMFCS level. Statistical analyses included χ 2 analysis and multiple logistic regression. RESULTS: One hundred sixty-three patients (326 hips) met the inclusion criteria, with TRC closure at age 14.0 (SD: 1.8) years. At final follow-up of 4.4 (SD: 2.4) years after TRC closure, 17% (55 hips), had a "more severe" FHS. From TRC closure to final follow-up, the frequencies of "less severe" hips decreased (-10%, P <0.001), while "more severe" increased (+115%, P <0.001). In multiple regression analysis, MP at TRC closure was the only significant risk factor associated with a "more severe" FHS at final follow-up ( P =0.03). Receiver operating characteristic curve analysis determined MP≥30.5% to be associated with a "more severe" FHS at final follow-up ( P <0.009). The FHS was not affected by reconstructive surgery, sex, GMFCS level, or intrathecal baclofen use. "Less severe" hips had lower Tönnis grades (0 to 1) compared with "more severe" hips (Tönnis grades 2 to 3) at final follow-up ( P <0.001). CONCLUSIONS: FHS at skeletal maturity was not influenced by prior reconstructive surgery but was negatively affected when MP≥30.5% at the time of TRC closure. The extent of residual femoral head deformity correlated with the severity of osteoarthritis at final follow-up. LEVEL OF EVIDENCE: Level III.
Asunto(s)
Parálisis Cerebral , Coxa Magna , Luxación de la Cadera , Osteoartritis , Niño , Humanos , Adolescente , Luxación de la Cadera/diagnóstico por imagen , Luxación de la Cadera/etiología , Luxación de la Cadera/cirugía , Parálisis Cerebral/complicaciones , Parálisis Cerebral/cirugía , Estudios Retrospectivos , Baclofeno , Resultado del TratamientoRESUMEN
BACKGROUND: Children with cerebral palsy (CP) frequently develop both neuromuscular hip dysplasia and scoliosis, and occasionally, the timing of the worsening of both of these pathologies is concurrent. The question as to whether the hip or spine should be addressed first in CP remains controversial, with the majority of evidence being "expert opinion." The purpose of this project was to determine the impact of posterior spinal fusion (PSF) on the change in hip displacement for children with CP without previous reconstructive hip surgery. METHODS: This was an Institutional Review Board-approved study that observed 67 patients from 2004 to 2018. Inclusion criteria included children with CP, 18 years of age and younger, Gross Motor Function Classification System IV and V, undergoing PSF at a single tertiary care children's hospital with a minimum 2-year follow-up. The primary outcome was the change in hip displacement as quantified by the migration percentage (MP). The hip with the highest MP (worst hip) at the spine preoperative analysis were included for analysis. Triradiate cartilage (TRC) status and pelvic obliquity correction were analyzed with multivariate analysis. RESULTS: Sixty-seven patients were included for analysis, with a mean age of 12.5±2.3 years. The mean major curve angle of the major curve was 77±23 degrees and the mean preoperative pelvic obliquity was 21±12 degrees. There was no statistically significant change in MP after PSF from a mean preoperative value of 41±27%, to a mean postoperative value of 41±29% at the last follow-up, (P=0.76) The mean follow-up time was 4.1±2.7 years. TRC status (P=0.52) and the severity of pelvic obliquity (P=0.10) did not statistically impact the change in MP after PSF. CONCLUSION: PSF did not influence-either negatively or positively-the progression of hip displacement in children with CP, regardless of pelvic obliquity correction or TRC status. The lack of deterioration in hip displacement post-PSF, however, may suggest a protective effect of spine surgery. LEVEL OF EVIDENCE: Level III-retrospective cohort study.
Asunto(s)
Parálisis Cerebral , Luxación de la Cadera , Escoliosis , Fusión Vertebral , Humanos , Niño , Adolescente , Luxación de la Cadera/etiología , Luxación de la Cadera/cirugía , Estudios Retrospectivos , Parálisis Cerebral/complicaciones , Parálisis Cerebral/cirugía , Resultado del Tratamiento , Escoliosis/cirugíaRESUMEN
BACKGROUND: Osteogenesis imperfecta (OI) is a genetic disorder characterized by brittle bones and long bone deformity. Realignment and intramedullary rodding with telescopic rods are indicated for progressive deformity and can help prevent fractures. Rod bending is a reported complication of telescopic rods and a common indication for revision; however, the fate of bent lower extremity telescopic rods in the setting of OI has not been reported. METHODS: Patients with OI at a single institution who underwent lower extremity telescopic rod placement with at least 1-year follow-up were identified. Bent rods were identified, and for these bone segments, we collected the location and angle of bend, subsequent telescoping, refracture, increasing angulation of bend, and date of revision. RESULTS: One hundred sixty-eight telescopic rods in 43 patients were identified. Forty-six rods (27.4%) bent during follow-up, with an average angulation of 7.3 (range: 1 to 24) degrees. In patients with severe OI, 15.7% of rods bent compared with 35.7% in nonsevere OI ( P =0.003). The proportion of bent rods was different between independent and nonindependent ambulators (34.1% and 20.5%; P =0.035). Twenty-seven bent rods (58.7%) were revised, with 12 rods (26.0%) revised early (within 90 d). The angulation of rods that were revised early was significantly higher than rods not (14.6 and 4.3 degrees, P <0.001). Of the 34 bent rods not revised early, the average time to revision or final follow-up was 29.1 months. Twenty-five rods (73.5%) continued to telescope, 14 (41.2%) increased in angulation (average 3.2 degrees), and 10 bones (29.4%) refractured. None of the refractures required immediate rod revision. Two bones had multiple refractures. CONCLUSIONS: Bending is a common complication of telescopic rods in the lower extremities of patients with OI. It is more common in independent ambulators and patients with nonsevere OI, possibly because of the increased demand placed on the rods. Rods with a small bend and maintained fixation can telescope and need not be an indication for immediate revision. LEVEL OF EVIDENCE: Level III-Retrospective review.
Asunto(s)
Fracturas Óseas , Osteogénesis Imperfecta , Niño , Humanos , Osteogénesis Imperfecta/cirugía , Osteogénesis Imperfecta/complicaciones , Fijadores Internos , Fracturas Óseas/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Migration percentage (MP) is widely used to evaluate hip stability in children with spastic cerebral palsy (CP). Orthopedic surgeons need more objective information to make a proper hip reconstruction surgical plan and predict the outcome. METHODS: Medical records and plain radiographs of children with CP who underwent the hip reconstruction procedure for dysplasia were reviewed retrospectively. RESULTS: In total, 253 operated hips (140 patients; 11.7 ± 3.3 years old) were included in this study. MP at pre-operative (Tpre) was 35.3 ± 22.5%; at immediate follow-up (Tpost) was 5.9 ± 9.5%; at last follow-up (Tfinal) was 9.8 ± 10.8% (4.5 ± 2.3 years post-operative at age 16.3 ± 2.8 years). In hips with Melbourne Cerebral Palsy Hip Classification Scale (MCPHCS) grade 3 (n = 78), around 30-45% had an unsatisfactory outcome at Tpost and Tfinal. However, hips categorized as other grades showed only 2.1-9.1% of unsatisfactory outcome. In less affected hips (pre-operative MP<30%, n = 122), 109 hips (89.3%) had varus derotation osteotomy only, the other 13 hips (10.7%) were combined with a pelvic osteotomy. In more severely affected hips (pre-operative MP ≥ 30%, n = 131), 26 hips (19.8%) had varus derotation osteotomy only, the other 105 hips (80.2%) were combined with a pelvic osteotomy. CONCLUSIONS: Hips with pre-operative MP between 15 and 29% (MCPHCS grades 3) can be a higher risk group of recurrent hip instability after hip reconstruction surgery. Multiple indications beyond MP should be considered when indicating pelvic osteotomy or hip muscle release as combined procedures with varus femoral osteotomy for hip reconstruction in this milder group to achieve a consistent long-term satisfactory outcome.
Asunto(s)
Parálisis Cerebral , Luxación de la Cadera , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Luxación de la Cadera/diagnóstico por imagen , Luxación de la Cadera/etiología , Luxación de la Cadera/cirugía , Estudios Retrospectivos , Espasticidad Muscular , Parálisis Cerebral/complicaciones , Parálisis Cerebral/cirugía , Osteotomía/métodos , Resultado del TratamientoRESUMEN
The objective of this study was to delineate a model for management of developmental dysplasia of the hip (DDH) treatment that incorporates hip ultrasound with objective/predicative parameters at key decision-making times. Hip sonograms of 74 infants (59 females, 15 males; 141 hips) with DDH were retrospectively reviewed. Hip sonographic score (HSS; ranges 0-10) was developed to reflect hip status based on sonographic position, stability, and morphology. Analysis on different management groups (i.e., no treatment, successful treatment, and failed treatment) showed that the trend of HSS is helpful in predicting course of the disease and determining effectiveness of treatment. A model for the management of DDH that utilizes an HSS and frequency schedule for hip sonography that is aligned with times of critical treatment decisions is proposed. This model illustrates how hip sonography can bring added value when timed to guide critical treatment decisions. (Journal of Surgical Orthopaedic Advances 32(1):047-054, 2023).
Asunto(s)
Displasia del Desarrollo de la Cadera , Luxación Congénita de la Cadera , Lactante , Masculino , Femenino , Humanos , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/terapia , Estudios Retrospectivos , UltrasonografíaRESUMEN
PURPOSE: The purpose of this study was to identify the incidence of venous thromboembolism (VTE) and characterize the demographics, comorbidities, and risk factors for patients with cerebral palsy (CP) having orthopaedic surgery. METHODS: All patients diagnosed with CP who underwent an orthopaedic surgical procedure at one institution between 2008 and 2017 were identified. Diagnosis codes and associated patient events were recovered from the electronic medical record. Each VTE event was reviewed to ascertain an actual VTE episode related to a surgical event. RESULTS: The review included 2583 orthopaedic surgical events in 1371 patients. Of the initial 88 cases identified, 28 cases had a deep thrombosis documented. Six cases of VTE occurred within 3 months following the surgical event. Three of these cases had thigh thrombosis, and 2 patients had upper arm thrombosis, and 1 patient had a superior vena cava thrombosis. On further workup, 5 of these 6 patients were identified as having a congenital hypercoagulable condition. CONCLUSIONS: VTE is a relatively rare occurrence after orthopaedic surgery in pediatric patients with CP, but when it occurs, a full hematologic workup for a congenital hypercoagulable condition is indicated. Based on the low incidence of thigh thrombosis, routine pharmacological or intermittent mechanical calf compression is not recommended. A careful clinical and family history should be performed to identify patients with possible genetic hypercoagulable conditions who would merit prophylaxis. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Parálisis Cerebral , Procedimientos Ortopédicos , Síndrome de la Vena Cava Superior , Tromboembolia Venosa , Trombosis de la Vena , Parálisis Cerebral/complicaciones , Parálisis Cerebral/epidemiología , Niño , Humanos , Incidencia , Procedimientos Ortopédicos/efectos adversos , Factores de Riesgo , Síndrome de la Vena Cava Superior/complicaciones , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Trombosis de la Vena/prevención & controlRESUMEN
BACKGROUND: The peroneal nerve is at risk when excising tumors in the proximal fibula. The rate of nerve injuries during proximal fibular tumor resection varies from 3% to 20%. Our goal was to report our experience with resection of osteochondromas in the proximal fibula and describe the technique and utility of neuromonitoring during excision of proximal fibular osteochondromas (PFO). METHODS: Patients with a diagnosis of symptomatic PFO who had undergone excision at one institution from 1994 to 2018 were included. An institutional review board-approved retrospective review was performed. Intraoperative neuromonitoring was provided from 2006 on by a single group utilizing a multimodality protocol. RESULTS: This study contains 29 patients who had excision of osteochondromas in the proximal fibula. Of these 29 consecutively monitored patients, there were 34 involved extremities. Intraoperative neuromonitoring alerts occurred in 10/29 (34.5%) procedures, which included 3 electromyography (EMG) (30%), 2 motor-evoked potential (20%), 1 somatosensory-evoked potential (10%), and 4 alerts with a combination of EMG/motor-evoked potential/somatosensory-evoked potential changes (40%). The interventions that were taken resulted in resolution of the neuromonitoring changes in all procedures. Postoperatively, we noted 2 (6.9%) new mild sensory deficits, which resolved during follow up. There were 3 patients in whom pre-existing sensory-motor deficits improved but not completely after surgery, 1 motor weakness, and 2 with residual paresthesia. In those initially presenting with paresis, there was improvement in 8 of the 8 extremities by the last follow-up visit. Pain as a symptom was resolved in all cases. There were no iatrogenic foot drop injuries. The average follow up was 32.2 months. CONCLUSIONS: Neuromonitoring during PFO excision demonstrated a high number of alerts, all of which resolved following timely corrective action. The use of neuromonitoring may help decrease the risk of iatrogenic postoperative neurological deficits following fibular osteochondroma surgery. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Neoplasias Óseas , Osteocondroma , Neoplasias Óseas/cirugía , Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Peroné , Humanos , Osteocondroma/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Growth modulation using tension band plates (TBPs) is increasingly important for lower limb deformity correction in patients with skeletal dysplasia (SKD). Development of rebound deformity is a concern after TBP removal. Data regarding this complication are rare; therefore, we evaluated the prevalence and risk factors for rebound deformity in children with SKD undergoing correction of genu valgum using TBP. METHODS: All patients with SKD with genu valgum treated by TBP at the distal femur or/and proximal tibia at a single center were reviewed. Inclusion criteria were: (1) minimum 2-year follow-up after TBP removal or having revision surgery for rebound deformity and (2) implant removal age for girls 14 years and below and boys 16 years and below. Exclusion criteria were any femoral/tibial osteotomies during TBP treatment or follow-up. A change of ≥3 degrees of mechanical lateral distal femoral and/or medial proximal tibial angle was accepted as rebound deformity and analyzed statistically. RESULTS: Thirty-three patients (59 limbs; 52 femur and 29 tibia physes) met our criteria. Mean follow-up after implant removal was 43.7 months. Rebound deformities were seen in 43 limbs (39 femurs and 13 tibias). Boys had more rebound than girls; however, this was not influenced by body mass index. Femurs had more rebound than tibias. Patients in the rebound group were younger than the nonrebound group. Time from application to removal of TBP was shorter in the rebound versus nonrebound group. Overcorrected limbs had more rebound deformity than not overcorrected. The difference in growth velocity of lower limbs in the rebound versus nonrebound group was statistically significant. Patients with epiphyseal dysplasia had more rebound than metaphyseal dysplasia, but this was not statistically significant. CONCLUSION: Risk factors for developing a rebound deformity after correction of genu valgum using TBP in SKD included male sex, TBP surgery at a young age, short duration of TBP implantation, overcorrected extremity (mechanical axis deviation ≤1), and high percent growth velocity after TBP removal. LEVEL OF EVIDENCE: Level IV-retrospective study.
Asunto(s)
Genu Valgum , Adolescente , Placas Óseas , Niño , Femenino , Fémur/cirugía , Genu Valgum/etiología , Genu Valgum/cirugía , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tibia/cirugíaRESUMEN
BACKGROUND: Early-onset scoliosis in children with skeletal dysplasia is progressive, contributing to cardiopulmonary restrictive disease. Serial elongation-derotation-flexion (EDF) casting, used in other etiologies of scoliosis to delay curve progression, may be beneficial in maximizing spine growth. Our hypothesis is serial EDF casting can be safely used as a temporary alternative to surgery, delaying progression and preserving growth, to treat scoliosis in skeletal dysplasia. METHODS: All patients with skeletal dysplasia treated at a single institution with serial EDF casting for scoliosis were reviewed retrospectively. Radiographic parameters: Cobb angle of major and minor curves, curve location, thoracic height, thoracolumbar height, space available for lung, and rib vertebra angle difference were measured before casting (C1), in first casting (C2), in last casting (C3), and out of last casting (C4). Peak inspiratory pressure (PIP) values were monitored and recorded during the casting application. RESULTS: Eleven patients met the inclusion criteria (mean 9.7 castings). The mean duration of EDF serial casting was 35 months. The mean major Cobb angles were 54 degrees° (C1), 30 degrees (C2), 37 degrees (C3), and 49 degrees (C4) with no statistically significant differences. The mean minor Cobb angles were 35 degrees (C1), 25 degrees (C2), 33 degrees (C3), and 51 degrees (C4) with no statistically significant differences. The mean thoracic heights were 130 mm (C1), 155 mm (C2), 173 mm (C3), and 160 mm (C4). The 19-mm mean difference between C2 and C3 represents spinal growth. The PIP-1, PIP-2, and PIP-3 mean values were 15, 27, and 18 cmH2O, respectively. Changes in PIP-1 and PIP-2 and PIP-2 and PIP-3 were statistically significant. CONCLUSION: Serial EDF casting can delay surgical scoliosis correction in children younger than 7 years with a diagnosis of skeletal dysplasia. Our study showed that serial casting controls progression of the major curve and allows longitudinal growth of the spine with possible expansion of lung volume for nearly 3 years. During cast application, PIP increased with molding and traction, and improved until windowing and trimming of the cast. LEVEL OF EVIDENCE: Level IV-retrospective study.