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BACKGROUND: Effective techniques for eliciting patients' preferences regarding their own care, when treatment options offer marginal gains and different risks, is an important clinical need. We sought to evaluate the association between patients' considerations of the time burdens of care ("time toxicity") with decisions about hypothetical treatment options. METHODS: We conducted a secondary analysis of a multicenter, mixed-methods study that evaluated patients' attitudes and preferences toward palliative-intent cancer treatments that delayed imaging progression-free survival (PFS) but did not improve overall survival (OS). We classified participants based on if they spontaneously volunteered one or more consideration of time burdens during qualitative interviews after treatment trade-off exercises. We compared the percentage of participants who opted for treatments with no PFS gain, some PFS gain, or who declined treatment regardless of PFS gain (in the absence of OS benefit). We conducted narrative analysis of themes related to time burdens. RESULTS: The study cohort included 100 participants with advanced cancer (55% women, 63% age > 60 years, 38% with gastrointestinal cancer, and 80% currently receiving cancer-directed treatment. Forty-six percent (46/100) spontaneously described time burdens as a factor they considered in making treatment decisions. Participants who mentioned time (vs not) had higher thresholds for PFS gains required for choosing additional treatments (P value .004). Participants who mentioned time were more likely to decline treatments with no OS benefit irrespective of the magnitude of PFS benefit (65%, vs 31%). On qualitative analysis, we found that time burdens are influenced by several treatment-related factors and have broad-ranging impact, and illustrate how patients' experiences with time burdens and their preferences regarding time influence their decisions. CONCLUSIONS: Almost half of participating patients spontaneously raised the issue of time burdens of cancer care when making hypothetical treatment decisions. These patients had notable differences in treatment preferences compared to those who did not mention considerations of time. Decision science researchers and clinicians should consider time burdens as an important attribute in research and in clinic.
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¼ Pediatric thoracolumbar trauma, though rare, is an important cause of morbidity and mortality and necessitates early, accurate diagnosis and management.¼ Obtaining a detailed history and physical examination in the pediatric population can be difficult. Therefore, the threshold for advanced imaging, such as magnetic resonance imaging, is low and should be performed in patients with head injuries, altered mental status, inability to cooperate with examination, and fractures involving more than 1 column of the spine.¼ The classification of pediatric thoracolumbar trauma is based primarily on adult studies and there is little high-level evidence examining validity and accuracy in pediatric populations.¼ Injury pattern and neurologic status of the patient are the most important factors when determining whether to proceed with operative management.
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Vértebras Lombares , Vértebras Torácicas , Humanos , Criança , Vértebras Torácicas/lesões , Vértebras Torácicas/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/diagnóstico por imagem , Traumatismos da Coluna Vertebral/terapia , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Traumatismos da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/terapia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Adolescente , Pré-EscolarRESUMO
BACKGROUND CONTEXT: The patient-reported outcomes measurement information system (PROMIS), created by the National institute of Health, is a reliable and valid survey for patients with lumbar spine pathology. Preoperative opioid use has been shown to be an important predictor variable of self-reported health status in legacy patient-reported outcome measures. PURPOSE: To investigate the impact of chronic preoperative opiate use on PROMIS survey scores. STUDY DESIGN: Retrospective database analysis. PATIENT SAMPLE: Between March 2019 and November 2021, 227 patients underwent lumbar decompression ± ≤ 2 level fusion. Fifty-seven patients (25.11%) had chronic preoperative opioid use. OUTCOME MEASURES: Oswestry disability index (ODI) and PROMIS survey scores. METHODS: A retrospective analysis of a prospectively maintained single center patient-reported outcome database was performed with a minimum of 2 year follow-up. PROMIS Anxiety, Depression, Fatigue, Pain Interference (PI), Physical Function (PF), Sleep disturbance (SD), and Social Roles (SR) surveys were recorded at preoperative intake with subsequent follow-up at 6, 12, and 24 months postoperatively. Patients were grouped into chronic opioid users as defined by >6-month duration of use. Differences in mean survey scores were evaluated using Welch t-tests. RESULTS: Two hundred and twenty-seven patients met our inclusion criteria of completed PROMIS surveys at the designated timepoints. A total of 57 (25.11%) were chronic opioid users (COU) prior to surgery. Analysis of patient-reported health outcomes shows that long term opioid use correlated with worse ODI and PROMIS scores at baseline compared to nonchronic users (NOU). At 1 and 2 year follow-up, the COU cohort continued to have significantly worse ODI, PROMIS Fatigue, PF, PI, SD, and SR scores. There is a statistical difference in the magnitude of change in health status between the 2 cohorts at 1 year follow-up in PROMIS Depression (-5.04±7.88 vs -2.49±8.73, p=.042), PF (6.25±7.11 vs 9.03±9.04, p=.019), and PI (-7.40±7.37 vs -10.58±9.87, p=.011) and 2 year follow-up in PROMIS PF (5.58±6.84 vs 7.99±9.64, p=.041) and PI (-6.71±8.32 vs -9.62±10.06, p=.032). Mean improvement in PROMIS scores for the COU cohort at 2 year follow-up exceeded minimal clinically important difference (MCID) in all domains except PROMIS Depression, SR and SD. CONCLUSION: Patients with chronic opioid use status have worse baseline PROMIS scores compared with patients who had nonchronic use. However, patients in the COU cohort displayed clinically significant postoperative improvement in multiple PROMIS domains. These results show that patients with chronic opioid use can benefit greatly from surgical intervention and will allow physicians to better set expectations with their patients.
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Analgésicos Opioides , Vértebras Lombares , Medidas de Resultados Relatados pelo Paciente , Humanos , Analgésicos Opioides/uso terapêutico , Masculino , Feminino , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Fusão Vertebral/efeitos adversos , Adulto , Descompressão CirúrgicaRESUMO
Solid tumor antibody-drug conjugates (ADC) have experienced more clinical success in the last 5 years than the previous 18-year span since the first ADC approval in 2000. While recent advances in protein engineering, linker design, and payload variations have played a role in this success, high expression and readily internalized targets have also been crucial to solid tumor therapy. However, these factors are also paradoxically connected to poor tissue penetration and lower efficacy. Previous work shows that potent ADCs can benefit from slower internalization under subsaturating doses to improve tissue penetration and increase tumor response. In contrast, faster internalization is predicted to increase efficacy under higher, tumor saturating doses. In this work, the intracellular delivery of SN-38 conjugated to an anti-carcinoembryonic antigen (anti-CEA) antibody (Ab) is increased by coadministering a noncompeting (cross-linking) anti-CEA Ab to improve efficacy in a colorectal carcinoma animal model. The SN-38 payload enables broad tumor saturation with clinically-tolerable doses, and under these saturating conditions, using a second CEA receptor cross-linking Ab yields faster internalization, which increases tumor killing efficacy. Our spheroid results show indirect bystander killing can also occur, but the more efficient direct cell killing from targeted intracellular payload release drives a greater tumor response. These results provide a strategy to increase therapeutic effectiveness with improved intracellular delivery under tumor saturating doses with the potential to expand the ADC target repertoire.
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Antineoplásicos , Imunoconjugados , Animais , Antígeno Carcinoembrionário , Irinotecano , Linhagem Celular Tumoral , Anticorpos MonoclonaisRESUMO
BACKGROUND: Printed educational materials (PEMs) have been used for patient education in various settings. The purpose of this study was to determine the readability, understandability, and actionability of trauma-related educational material from the Pediatric Orthopaedic Society of North America (POSNA, Orthokids), as well as determine its efficacy in educating pediatric orthopaedic trauma patients and caregivers. METHODS: The readability, understandability and actionability of PEMs was assessed using the Patient Education materials Assessment Tool (PEMAT). Five reviewers ranging in experience independently evaluated the educational materials. The efficacy of PEMs was assessed prospectively by randomizing patients into 2 groups. The first group (Education) received the OrthoKids educational material related to the patient's fracture. The second group (No Education) did not receive the educational material. At the first follow-up visit, parents/guardians in both groups completed surveys. Statistical analyses included descriptive and univariate statistics. RESULTS: The understandability of PEMs was similar (68% to 74%); however, the educational materials had varying actionability scores ranging from 20% for femoral shaft fractures to 60% for elbow fractures. In total, 101 patients were randomized to assess the efficacy of educational materials (Education=51, No Education=50). There were no significant differences in sex, age, race/ethnicity, and level of education between caregivers in both groups ( P > 0.05). Only 61% (31/51) participants in the Education group reported using the educational material; however, 67% to 68% of participants in either group reported wanting PEMs. Participants in the group that did not receive PEMs were significantly more likely to use the internet to find more information (74% vs. 51%, P < 0.05). CONCLUSIONS: This study suggests that participants that did not receive PEMs were significantly more likely to search the internet for more information. Improving the quality and actionability of educational resources on electronic platforms is needed to improve patient education. A multi-modal approach using PEMs that includes a list of high-quality online sources would likely be most effective in educating pediatric trauma patients and caregivers. LEVEL OF EVIDENCE: I.
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Letramento em Saúde , Ortopedia , Humanos , Criança , Educação de Pacientes como Assunto , Materiais de Ensino , Escolaridade , Compreensão , InternetRESUMO
BACKGROUND: Assessment of prognostic awareness (PA) in patients with advanced cancer is challenging because patient responses often indicate their hopes. The objectives of this scoping review were to summarize studies that measured PA in patients with advanced cancer and to synthesize data about how PA was measured and whether hope was incorporated into the measurement. METHODS: MEDLINE and Embase databases were searched from inception to December 14, 2021. Data regarding the impact of hope on assessment of PA were extracted when studies reported on patients' beliefs about prognosis and patients' beliefs about their doctor's opinion about prognosis. An interpretive synthesis approach was used to analyze the data and to generate a theory regarding the incorporation of hope into the assessment of PA. RESULTS: In total, 52 studies representing 23â766 patients were included. Most were conducted in high-income countries and measured PA based on the goal of treatment (curable vs incurable). Five studies incorporated hope into the assessment of PA and reported that among patients who responded that their treatment goal was a cure, an average of 30% also acknowledged that their doctors were treating them with palliative intent. Interpretive synthesis of the evidence generated a trinary conceptualization of PA patients who are aware and accepting of their prognosis; aware and not accepting; and truly unaware. Each of these groups will benefit from different types of interventions to support their evolving PA. CONCLUSION: The trinary conceptualization of PA may promote understanding of the impact of hope in the assessment of PA and guide future research.
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Neoplasias , Qualidade de Vida , Humanos , Prognóstico , Neoplasias/diagnóstico , Neoplasias/terapia , Cuidados PaliativosRESUMO
46,XX individuals born with severely masculinized genitals due to congenital adrenal hyperplasia (CAH) who have been assigned male at birth and reared male can successfully establish a male gender identity/role, find employment, marry, function sexually with a female partner, and develop positive mental health status. While there were a few individuals who reportedly did not fare well or who changed gender to female, the majority of those identifying as males appear to have an overall good quality of life. Parental/family support, along with the support of others, appears essential to a positive outcome as a male, or as a female. This paper suggests that serious consideration should be given to male gender assignment and rearing and, in certain situations, is justified. Disorders of sex differentiation teams should inform parents about the option for male assignment and rearing in 46,XX CAH infants with severe genital masculinization, which is a rare condition. To provide this option is concordant with the principles of ethics, transparency and with the Endocrine Society Guidelines and the American Academy of Pediatrics' policy of fully informed consent.
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Hiperplasia Suprarrenal Congênita , Humanos , Masculino , Recém-Nascido , Feminino , Identidade de GêneroRESUMO
STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare patient-reported physical activity between anterior thoracic vertebral body tethering and posterior lumbar spine tethering (ATVBT/PLST) and posterior spinal instrumentation and fusion (PSIF) with minimum 2 year follow-up. METHODS: Consecutive skeletally immature patients with idiopathic scoliosis and a thoracic and lumbar curve magnitude ≥40° who underwent either ATVBT/PLST or PSIF from 2015-2019 were included. The primary outcome was rate of returning to sport. Secondary outcomes included ability to bend and satisfaction with sport performance as well as weeks until return to sport, school, physical education (PE) classes, and running. RESULTS: Ten patients underwent ATVBT/PLST and 12 underwent PSIF. ATVBT/PLST patients reported significantly faster return to sport (13.5 weeks vs 27.9 weeks, P = .04), running (13.3 weeks vs 28.8 weeks, P = .02), and PE class (12.6 weeks vs 26.2 weeks, P = .04) compared to PSIF patients. ATVBT/PLST patients reported that they had to give up activities due to their ability to bend at lower rates than PSIF patients while reporting "no changes" in their ability to bend after surgery at higher rates than PSIF patients (0% vs 4% giving up activities and 70% vs 0% reporting no changes in bending ability for ATVBT/PLST and PSIF, respectively, P = .01). Compared to PSIF patients, ATVBT/PLST patients experienced less main thoracic and thoracolumbar/lumbar curve correction at most recent follow-up (thoracic: 41 ± 19% vs 69 ± 18%, P = .001; thoracolumbar/lumbar: 59 ± 25% vs 78 ± 15%, P = .02). No significant differences in the number of revision surgeries were observed between ATVBT/PLST and PSIF patients (4 (40%) and 1 (8%) for ATVBT/PLST and PSIF, respectively, P = .221). CONCLUSIONS: ATVBT/PLST patients reported significantly faster rates of returning to sport, running, and PE. In addition, ATVBT/PLST patients were less likely to have to give up activities due to bending ability after surgery and reported no changes in their ability to bend after surgery more frequently than PSIF patients. However, the overall rate of return to the same or higher level of sport participation was high amongst both groups, with no significant difference observed between ATVBT/PLST and PSIF patients.
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PURPOSE: To review existing classification systems for degenerative spondylolisthesis (DS), propose a novel classification designed to better address clinically relevant radiographic and clinical features of disease, and determine the inter- and intraobserver reliability of this new system for classifying DS. METHODS: The proposed classification system includes four components: 1) segmental dynamic instability, 2) location of spinal stenosis, 3) sagittal alignment, and 4) primary clinical presentation. To establish the reliability of this system, 12 observers graded 10 premarked test cases twice each. Kappa values were calculated to assess the inter- and intraobserver reliability for each of the four components separately. RESULTS: Interobserver reliability for dynamic instability, location of stenosis, sagittal alignment, and clinical presentation was 0.94, 0.80, 0.87, and 1.00, respectively. Intraobserver reliability for dynamic instability, location of stenosis, sagittal alignment, and clinical presentation were 0.91, 0.88, 0.87, and 0.97, respectively. CONCLUSION: The UCSF DS classification system provides a novel framework for assessing DS based on radiographic and clinical parameters with established implications for surgical treatment. The almost perfect interobserver and intraobserver reliability observed for all components of this system demonstrates that it is simple and easy to use. In clinical practice, this classification may allow subclassification of similar patients into groups that may benefit from distinct treatment strategies, leading to the development of algorithms to help guide selection of an optimal surgical approach. Future work will focus on the clinical validation of this system, with the goal of providing for more evidence-based, standardized approaches to treatment and improved outcomes for patients with DS.
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PURPOSE OF REVIEW: Scheuermann's kyphosis (SK) is a developmental deformity of the spine that affects up to 8% of children in the US. Although, the natural progression of SK is noted to be gradual over years, severe deformity can be associated with significant morbidity. Thorough clinical examination and interpretation of relevant imaging help differentiate and confirm this diagnosis. Treatment includes both operative and nonoperative approaches. The purpose of this article is to provide an updated overview of the current theories of its pathogenesis, as well as the principles of diagnosis and treatment of SK. RECENT FINDINGS: Although a definitive, unified theory continues to be elusive, numerous reports in the past decade provide insight into the pathophysiology of SK. These include alterations in mechanical stress and/or hormonal disturbances. Candidate genes have also been identified to be linked to the inheritance of SK. Updates to nonoperative treatment include the effectiveness of dedicated exercise programs, as well as the types and duration of orthotic treatment. Advances in surgical technique can be observed with a trend toward a posterior-only approach, with supporting evidence for careful evaluation of both the sagittal and coronal planes to determine fusion levels in order to avoid postoperative junctional pathologies. SK is an important cause of structural or rigid kyphosis. It can lead to significant morbidity in severe cases. Treatment is based on curve magnitude and symptoms. Nonoperative treatment consists of physical therapy in symptomatic patients, and bracing can be added for skeletally mature patients. Operative management can be considered in patients with large, progressive, and symptomatic deformity. Future studies can benefit from a focused investigation into patient-reported outcomes after undergoing appropriate treatment.
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BACKGROUND: Cancer patients' attitudes toward progression-free survival (PFS) gains offered by treatment are not well understood, particularly in the absence of overall survival (OS) gains. The objectives were to describe patients' willingness to accept treatment that offers PFS gains without OS gains, to compare these findings with treatments offering OS gains, and to qualitatively summarize patients' reasons for their preferences. METHODS: A multicenter, cross-sectional, convergent mixed-methods study design recruited patients who had received at least 3 months of systemic therapy for incurable solid tumors. A treatment trade-off exercise determined the gains in imaging PFS that patients require to prefer additional systemic treatment for a scenario of a newly diagnosed, asymptomatic, incurable abdominal tumor. A qualitative, descriptive, thematic analysis explored factors influencing patients' decisions, and a narrative method integrated the quantitative and qualitative findings. RESULTS: In total, 100 patients participated (63% were older than 60 years of age). If additional treatment with added toxicity offered no OS advantage, 17% would prefer it for no PFS benefit; 26% for some PFS benefit (range, 3-9 months), whereas 51% would decline it regardless of PFS benefit. Similarly, 71% preferred additional treatment offering a 6-month OS advantage dependent on described toxicity levels (P = .03). A spectrum of reasons for these preferences reflected the complexity of participants' attitudes and values. CONCLUSIONS: Prolongation of time to progression was not universally valued. Most patients did not prefer treatments that negatively affect quality of life for PFS gains alone. Implications for individual decision making, policy, and trials research are discussed.
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Neoplasias , Qualidade de Vida , Humanos , Estudos Transversais , Neoplasias/terapia , Intervalo Livre de Progressão , Progressão da Doença , Intervalo Livre de DoençaRESUMO
Background: Social determinants of health (SDOH), have been demonstrated to significantly impact health outcomes in spine patients. There may be interaction between opioid use and these factors in spine surgical patients. We aimed to evaluate the social determinants of health (SDOH) which are associated with perioperative opioid use among lumbar spine patients. Methods: This retrospective cohort study included patients undergoing spine surgery for lumbar degeneration in 2019. Opioid use was determined based on prescription records from the electronic medical records. Preoperative opioid users (OU) were compared with opioid-naïve patients regarding SDOH including demographics like age and race, and clinical data such as activity and tobacco use. Demographics and surgical data, including age, comorbidities, surgical invasiveness, and other variables were also collected from the records. Multivariate logistic regression was used for analysis of these factors. Results: Ninety-eight patients were opioid-naïve and 90 used opioids preoperatively. All OU had ≥3 months of use, had more prior spine surgeries (1.07 vs. 0.44, p<.001) and more comorbidities including diabetes, hypertension, and depression (p=.021, 0.043, 0.017). Patients from lower community median income areas, unemployed, or with lower physical capacity (METS<5) were more likely to use opioids preoperatively. Postoperative opioid use was strongly associated with preoperative opioid use, as well as alcohol use, and lower community median income. At one year postoperatively, OU had higher rates of opioid use [72.2% vs. 15.3%, p<.001]. Conclusions: Unemployment, low physical activity level, and lower community median income were associated with preoperative opioid use and longer-term opioid use postoperatively.
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BACKGROUND: Septic arthritis of the knee in children is a challenging problem. Surgical debridement is an established treatment, but there is a paucity of literature on long-term prognosis. AIM: To determine the rates and factors associated with return to surgery (RTS) and readmission after index surgical debridement for septic arthritis of the knee in children. METHODS: This is a retrospective cohort study that utilizes data from the Healthcare Cost and Utilization Project (HCUP). We included patients between ages 0 to 18 years that underwent surgical debridement for septic arthritis of the knee between 2005 and 2017. Demographic data included age, gender, race, hospital type and insurance type. Clinical data including index admission length of stay (LOS) and Charlson Comorbidity Index (CCI) were available from the HCUP database. Descriptive statistics were used to summarize the data and univariate and multivariate analyses were performed. RESULTS: Nine-hundred thirty-two cases of pediatric septic knee were included. This cohort was 62.3% male, with mean age of 9.0 (± 6.1) years. Approximately 46% of patients were white and approximately half had Medicaid insurance. Thirty-six patients (3.6%) required RTS at a minimum of 2 year after index surgery, and 172 patients (18.5%) were readmitted at any point. The mean readmission LOS was 11.6(± 11.3) d. Higher CCI was associated with RTS (P = 0.041). There were no significant associations in age, gender, race, insurance type, or type of hospital to which patients presented. Multivariate analysis showed that both increased CCI (P = 0.008) and shorter LOS (P = 0.019) were predictive of RTS. CONCLUSION: Septic arthritis of the knee is an important condition in children. The CCI was associated with RTS at a minimum of 2 years after index procedure. No association was found with age, gender, race, insurance type, or hospital type. Shorter LOS and CCI were associated with RTS in multivariate analysis. Overall, risk of subsequent surgery and readmission after pediatric septic knee arthritis is low, and CCI and shorter LOS are predictive of RTS.
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In this randomized pilot study, we examined the effects of yoga intervention on axial and peripheral bone mineral density (BMD), disordered eating cognitions, anxiety, and depression in adolescent girls with anorexia nervosa (AN). Fifteen young women aged 13-18 years with AN or atypical AN were randomized to either a Yoga group (n = 7), including twice-weekly yoga for 24 weeks plus standard outpatient care, or Non-Yoga group (n = 8), who received standard outpatient care alone. Data from anthropometrics, mental health and eating behavior questionnaires, dual-energy x-ray absorptiometry, and peripheral quantitative computed tomography measurements were obtained at baseline and 6 months. The adjunct of yoga to standard treatment resulted in statistically significant improvement of axial BMD, depression, and disordered eating cognitions in comparison to the Non-Yoga group. In conclusion, a gentle yoga intervention may be beneficial for improving bone and mental health in adolescent females with AN.
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Anorexia Nervosa , Feminino , Humanos , Adolescente , Anorexia Nervosa/terapia , Anorexia Nervosa/psicologia , Projetos Piloto , Saúde Mental , Densidade Óssea , Absorciometria de FótonRESUMO
¼: Halo-gravity traction (HGT) is a well-established technique for correcting severe spinal deformity in pediatric patients. ¼: HGT induces soft-tissue relaxation and gradually lengthens the spine, and it can be used preoperatively and intraoperatively. ¼: It is typically indicated for spinal deformity over 90° in any plane and medical optimization. ¼: There are several complications associated with the use of HGT, and it is critical to follow a protocol and perform serial examinations to minimize this risk.
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Tração , Criança , Humanos , Exame Físico , Coluna Vertebral/cirurgiaRESUMO
PURPOSE: While posterior spinal instrumentation and fusion (PSIF) for severe adolescent idiopathic scoliosis (AIS) is the gold standard, anterior vertebral body tethering (AVBT) is becoming an alternative for select cases. Several studies have compared technical outcomes for these two procedures, but no studies have compared post-operative pain and recovery. METHODS: In this prospective cohort, we evaluated patients who underwent AVBT or PSIF for AIS for a period of 6 weeks after operation. Pre-operative curve data were obtained from the medical record. Post-operative pain and recovery were evaluated with pain scores, pain confidence scores, PROMIS scores for pain behavior, interference, and mobility, and functional milestones of opiate use, independence in activities of daily living (ADLs), and sleeping. RESULTS: The cohort included 9 patients who underwent AVBT and 22 who underwent PSIF, with a mean age of 13.7 years, 90% girls, and 77.4% white. The AVBT patients were younger (p = 0.03) and had fewer instrumented levels (p = 0.03). Results were significant for decreased pain scores at 2 and 6 weeks after operation (p = 0.004, and 0.030), decreased PROMIS pain behavior at all time points (p = 0.024, 0.049, and 0.001), decreased pain interference at 2 and 6 weeks post-operative (p = 0.012 and 0.009), increased PROMIS mobility scores at all time points (p = 0.036, 0.038, and 0.018), and faster time to functional milestones of weaning opiates, independence in ADLs, and sleep (p = 0.024, 0.049, and 0.001). CONCLUSION: In this prospective cohort study, the early recovery period following AVBT for AIS is characterized by less pain, increased mobility, and faster recovery of functional milestones, compared with PSIF. LEVEL OF EVIDENCE: IV.
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Cifose , Escoliose , Feminino , Humanos , Adolescente , Masculino , Escoliose/cirurgia , Estudos Prospectivos , Corpo Vertebral , Atividades Cotidianas , Dor Pós-OperatóriaRESUMO
Antibody-drug conjugates (ADC) are a rapidly growing class of targeted cancer treatments, but the field has experienced significant challenges from their complex design. This study examined the multiscale distribution of sacituzumab govitecan (SG; Trodelvy), a recently clinically approved ADC, to clarify the mechanism(s) of efficacy given its unique design strategy. We employed a multiscale quantitative pharmacokinetic approach, including near-infrared fluorescence imaging, single-cell flow cytometry measurements, payload distribution via γH2AX pharmacodynamic staining, and a novel dual-labeled fluorescent technique to track the ADC and payload in a high trophoblast cell-surface antigen 2 expression xenograft model of gastric cancer (NCI-N87). We found that rapid release of the SN-38 payload from the hydrolysable linker inside cells imparts more DNA damage in vitro and in vivo than an ADC with a more stable enzyme cleavable linker. With SG, little to no extracellular payload release in the tumor was observed using a dual-labeled fluorescence technique, although bystander effects were detected. The high dosing regimen allowed the clinical dose to reach the majority of cancer cells, which has been linked to improved efficacy. In addition, the impact of multiple doses (day 1 and day 8) of a 21-day cycle was found to further improve tissue penetration despite not changing tumor uptake [percent injected dose per gram (%ID/g)] of the ADC. These results show increased ADC efficacy with SG can be attributed to efficient tumor penetration and intracellular linker cleavage after ADC internalization. This quantitative approach to study multiscale delivery can be used to inform the design of next-generation ADCs and prodrugs for other targets.
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Imunoconjugados , Neoplasias Gástricas , Humanos , Liberação Controlada de Fármacos , Camptotecina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular TumoralRESUMO
CASE: Congenital Zika syndrome (CZS) has been noted after the South American pandemic of Zika virus which peaked in 2015 to 2016, and the associated sequelae are still being described. Scoliosis has been noted in patients with CZS; however, there is a paucity of literature on the prevalence or management of scoliosis secondary to this condition. We report the case of a 5-year-old girl with severe neuromuscular scoliosis due to CZS that was managed with halo-gravity traction, followed by a growth-friendly construct. CONCLUSION: This case report highlights the need for more research focusing on the survivors of the Zika pandemic.
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Doenças Neuromusculares , Escoliose , Fusão Vertebral , Infecção por Zika virus , Zika virus , Feminino , Humanos , Pré-Escolar , Escoliose/cirurgia , Escoliose/complicações , Infecção por Zika virus/complicações , Infecção por Zika virus/congênito , Infecção por Zika virus/epidemiologia , Tração/efeitos adversos , Fusão Vertebral/efeitos adversosRESUMO
BACKGROUND: Infectious illness is the biggest cause of death in children due to a physical illness, particularly in children under five years. If mortality is to be reduced for this group of children, it is important to understand factors affecting their pathways to hospital. The aim of this study was to retrospectively identify organisational and environmental factors, and individual child, family, and professional factors affecting timing of admission to hospital for children under five years of age with a serious infectious illness (SII). METHODS: An explanatory modified grounded theory design was used in collaboration with parents. Two stages of data collection were conducted: Stage 1, interviews with 22 parents whose child had recently been hospitalised with a SII and 14 health professionals (HPs) involved in their pre-admission trajectories; Stage 2, focus groups with 18 parents and 16 HPs with past experience of SII in young children. Constant comparative analysis generated the explanatory theory. RESULTS: The core category was 'navigating uncertain illness trajectories for young children with serious infectious illness'. Uncertainty was prevalent throughout the parents' and HPs' stories about their experiences of navigating social rules and overburdened health services for these children. The complexity of and lack of continuity within services, family lives, social expectations and hierarchies provided the context and conditions for children's, often complex, illness trajectories. Parents reported powerlessness and perceived criticism leading to delayed help-seeking. Importantly, parents and professionals missed symptoms of serious illness. Risk averse services were found to refer more children to emergency departments. CONCLUSIONS: Parents and professionals have difficulties recognising signs of SII in young children and can feel socially constrained from seeking help. The increased burden on services has made it more difficult for professionals to spot the seriously ill child.