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Introduction: For infants with ulnar polydactyly, surgical removal of the supernumerary digit can be performed under general or local anesthetic. This study evaluated the wait times, surgical duration, and sedation times associated with performing the procedure under local versus general anesthetic in infants with ulnar polydactyly. Methods: The databases of three surgeons at our institution were reviewed for children less than 2 years of age who underwent surgery for non-syndromic ulnar polydactyly. Data collection included patient demographics, wait times, duration of surgery and sedation and complications. Results: The study included children (n = 55) who received treatment under local (n = 22) or general (n = 33) anesthesia. The wait times for the local anesthetic group were significantly shorter than the general anesthetic group (p < 0.05) for: referral to first consultation appointment; referral to surgery date, and decision date to surgery date. The duration of surgery (17.9 ± 6.9 vs 36.6 ± 20.2 min) and sedation time (26.3 ± 11.1 vs 74.8 ± 29.1 min) were significantly shorter in the local anaesthetic group (p < 0.05). There were no differences in complication rates between the groups. Conclusion: In this single-institution retrospective analysis, treatment of non-syndromic ulnar polydactyly with local anesthetic and bottle sedation was associated with shorter wait times, and duration of surgery and sedation. Level of Evidence: III, retrospective chart review and quality improvement initiative.
Introduction : Chez les nourrissons présentant une polydactylie cubitale, il est possible de procéder à l'ablation chirurgicale du doigt excédentaire sous anesthésie locale ou générale. La présente étude visait à évaluer les temps d'attente, la durée de l'opération et la durée de la sédation associés à l'intervention lorsqu'elle était effectuée sous anesthésie locale ou générale chez les nourrissons présentant une polydactylie cubitale. méthodes : Les chercheurs ont fouillé les bases de données de trois chirurgiens de leur établissement pour en extraire les cas d'enfants de moins de deux ans ayant subi une opération de la polydactylie cubitale non syndromique. La collecte de données incluait les caractéristiques des patients, les temps d'attente, la durée de l'opération et de la sédation et les complications. Résultats : La présente étude incluait des enfants (n=55) qui avaient été traités sous anesthésie locale (n=22) ou générale (n=33). Le temps d'attente du groupe sous anesthésie locale était beaucoup plus court que celui du groupe sous anesthésie générale (p<0,05) pour ce qui est de la période entre l'orientation et la première consultation, l'orientation et la date de l'opération, ainsi que la date de la décision et la date de l'opération. La durée de l'opération (17,9 ± 6,9 minutes par rapport à 36,6 ± 20,2 minutes) et de la sédation (26,3 ± 11,1 minutes par rapport à 74,8 ± 29,1 minutes) était beaucoup plus courte dans le groupe sous anesthésie locale (p<0,05). Il n'y avait pas de différence entre les groupes à l'égard des taux de complications. Conclusion : Dans cette analyse rétrospective mono-institutionnelle, le traitement de la polydactylie cubitale non syndromique accompagné d'une anesthésie locale et d'une sédation par bonbonne était associé à une diminution du temps d'attente ainsi que de la durée d'opération et de sédation.
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Cell line development (CLD) represents a complex but highly critical process during the development of a biological drug. To shed light on this crucial workflow, a team of BioPhorum members (authors) has developed and executed surveys focused on the activities and effort involved in a typical CLD campaign. An average of 27 members from different companies that participate in the BioPhorum CLD working group answered surveys covering three distinguishable stages of a standard CLD process: (1) Pre-transfection, including vector design and construction; (2) Transfection, spanning the initial introduction of vector into cells and subsequent selection and analysis of the pools; and (3) Single Cell Cloning and Lead Clone Selection, comprising methods of isolating single cells and confirming clonal origin, subsequent expansion and screening processes, and methods for identifying and banking lead clones. The surveys were very extensive, including a total of 341 questions split between antibody and complex molecule CLD processes. In this survey review, the authors interpret and highlight responses for antibody development and, where relevant, contrast complex molecule development challenges to provide a comprehensive industry perspective on the typical time and effort required to develop a CHO production cell line.
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BACKGROUND: Elbow flexion contracture development in school-age children with a brachial plexus birth injury (BPBI) is common. Reports indicate onset between 2 and 4 years; however, little is known about early childhood prevalence, development, and trajectory of these contractures. PURPOSE: To determine the prevalence and predictors of BPBI elbow flexion contractures during early childhood. STUDY DESIGN: A retrospective cross-sectional study. METHODS: Demographic, diagnostic, treatment, and elbow contracture data were collected for children with a BPBI <4 years between 2015 and 2019 from a prospectively collected database. Spinal root motor contributions and injury were determined using Active Movement Scale (AMS) scores at 6 weeks of age and used to predict contracture development. RESULTS: Of the 171 children that met inclusion criteria, 87% (n = 149) had upper plexus injuries. The mean age at the time of evaluation for an elbow contracture was 21.4 ± 12.7 months. The prevalence of elbow flexion contractures was 22% (n = 38), with mean onset at 13.4 ± 11.0 months. Mean contracture degree was -10.8 ± -6.9 degrees with 76% (n = 29) <-10 degrees. AMS shoulder abduction, flexion, and external rotation; elbow flexion; forearm supination; and wrist extension scores at a mean 2.3 ± 1.4 months were significantly lower in children who developed elbow flexion contractures (p < 0.001). Logistic regression found that low AMS elbow flexion with high elbow extension scores were a significant (p < 0.003) predictor of elbow contracture development. CONCLUSIONS: The prevalence of elbow flexion contractures in early childhood is greater than previously understood. These findings indicate that C5-C6 injury affecting elbow flexion with relative preservation of elbow extension is a predictor of contracture development. Further research is needed to investigate the nature and sequelae of C5-C6 injury and its effects on elbow flexion contracture development.
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BACKGROUND: Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients; however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. METHODS: A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale scores, Cookie tests, and the requirement for subsequent neuroma resection and nerve grafting. RESULTS: Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie test for elbow flexion. Thirteen patients either passed the Cookie test or scored Active Movement Scale score 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie test. Two patients did not have sufficient follow-up to assess elbow flexion. CONCLUSION: Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.
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Traumatismos del Nacimiento , Neuropatías del Plexo Braquial , Plexo Braquial , Contractura , Neuroma , Lactante , Humanos , Neuropatías del Plexo Braquial/cirugía , Plexo Braquial/lesiones , Neuroma/cirugía , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
BACKGROUND: The Sup-ER protocol involves a repositioning program for infants with brachial plexus birth injury to position the shoulder in external rotation (ER) to address progressive loss in passive range of motion (PROM). The British Columbia Children's Hospital (BCCH) eligibility criteria for this protocol are infants aged 4-8 weeks with decreased shoulder ER PROM and/or Active Movement Scale (AMS) shoulder ER and/or supination scores ≤2. The resources needed to implement this protocol in large clinics have not been studied. PURPOSE: This study aims to evaluate the BCCH criteria that are used to identify appropriate candidates for the Sup-ER protocol. STUDY DESIGN: A retrospective cohort study was conducted to identify the percentage of infants who would have been recommended the Sup-ER protocol based on their PROM and AMS scores between 4 and 8 weeks of age. METHODS: A sensitivity and specificity evaluation was used to describe the BCCH criteria's ability to identify infants in this historical cohort who went on to have incomplete shoulder function (ie, true positive) vs infants who had functional shoulder outcome at 9 months of age (ie, false positive). RESULTS: At a mean of 5.8 weeks (95% confidence interval [CI] 5.3, 6.3), 46 of the 87 (53%) infants satisfied the BCCH Sup-ER protocol criteria. Forty-four (51%) were female, half (n = 45) were left side affected, and 88% had upper plexus injury. The BCCH Sup-ER protocol criteria had sensitivity of 100% and specificity of 71% to identify infants with incomplete shoulder function. Removing the AMS supination ≤2 score criterion from the criteria improves the specificity to 84%, while sensitivity remains high (97%). CONCLUSIONS: Modifying the BCCH criteria to all infants aged 4-8 weeks with AMS shoulder ER ≤2 and/or decreased shoulder ER PROM improves the precision of identifying infants who would benefit from the Sup-ER protocol.
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Traumatismos del Nacimiento , Neuropatías del Plexo Braquial , Plexo Braquial , Articulación del Hombro , Lactante , Niño , Humanos , Femenino , Masculino , Neuropatías del Plexo Braquial/diagnóstico , Estudios Retrospectivos , Estudios de Factibilidad , Rango del Movimiento Articular , Plexo Braquial/lesiones , Resultado del TratamientoRESUMEN
This study describes mental health and psychosocial screening processes, access to care and interventions provided to children with upper limb musculoskeletal conditions. A cross-sectional e-survey study was conducted of 107 healthcare professionals who work with children with congenital hand and upper limb differences and brachial plexus birth injuries. Of them, 41 (38%) reported that they routinely screen for mental health and psychosocial concerns. Few (12%) reported the use of standardized outcome measures. In total, 51 (48%) healthcare professionals reported that there was a waiting list for mental health services at their institution. Collectively, healthcare professionals were unsatisfied with the staffing, access to care and types of interventions available. Reported barriers to care included the growing need for mental health support, lack of resources and poor continuity of care after referrals. Future research should focus on identifying and validating a mental health screening tool and investigating the processes affecting access to mental health care.Level of evidence: IV.
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This article describes the approach utilized by the multidisciplinary team at Sick Kids Hospital to evaluate and treat patients with brachial plexus birth injury (BPBI). This approach has been informed by more than 30 years of experience treating over 1,800 patients with BPBI and continues to evolve over time. The objective of this article is to provide readers with a practical overview of the Sick Kids approach to the management of infants with BPBI.
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LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe methods of clinical evaluation for neurologic recovery in brachial plexus birth injury. 2. Understand the role of different diagnostic imaging modalities to evaluate the upper limb. 3. List nonsurgical strategies and surgical procedures to manage shoulder abnormality. 4. Explain the advantages and disadvantages of microsurgical nerve reconstruction and distal nerve transfers in brachial plexus birth injury. 5. Recognize the prevalence of pain in this population and the need for greater sensory outcomes evaluation. SUMMARY: Brachial plexus birth injury (BPBI) results from closed traction injury to the brachial plexus in the neck during an infant's vertex passage through the birth canal. Although spontaneous upper limb recovery occurs in most instances of BPBI, some infants do not demonstrate adequate motor recovery within an acceptable timeline and require surgical intervention to restore upper limb function. This article reviews major advances in the management of BPBI in the past decade that include improved understanding of shoulder pathology and its impact on observed motor recovery, novel surgical techniques, new insights in sensory function and pain, and global efforts to develop standardized outcomes assessment scales.
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Traumatismos del Nacimiento , Neuropatías del Plexo Braquial , Plexo Braquial , Transferencia de Nervios , Lactante , Humanos , Neuropatías del Plexo Braquial/diagnóstico , Neuropatías del Plexo Braquial/etiología , Neuropatías del Plexo Braquial/cirugía , Traumatismos del Nacimiento/complicaciones , Traumatismos del Nacimiento/cirugía , Plexo Braquial/cirugía , Plexo Braquial/lesiones , Procedimientos Neuroquirúrgicos/métodos , Transferencia de Nervios/métodosRESUMEN
SUMMARY: The success of conjoined twin separation has increased since the 1950s, notwithstanding the numerous technical and physiologic challenges encountered in such procedures. Together with improvements in our understanding of conjoined twin physiology and the accumulation of surgical expertise, technological advances have largely paralleled the improvement in outcomes. In particular, advances in imaging modalities, adjuncts to abdominal wall closure such as mesh and tissue expansion, and three-dimensional modeling have been instrumental in advancing care for these patients. Considered together, these domains have allowed multidisciplinary teams to better delineate conjoined anatomy, facilitated improved surgical planning and decision-making, and assisted in overcoming the frequent challenges associated with soft-tissue closure. This review delineates the improvements in these modalities and their relationship to increasingly successful conjoined twin separation in recent years.
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Gemelos Siameses , Abdomen/cirugía , Humanos , Tecnología , Expansión de Tejido/métodos , Gemelos Siameses/cirugíaRESUMEN
BACKGROUND: A common sequela of brachial plexus birth injury (BPBI) is an elbow flexion contracture. Youth with BPBI and their families face rehabilitation or surgical decisions that ideally entail careful deliberation of the risks and benefits of treatment within the context of the child's and family's functional and appearance-related goals. OBJECTIVE: To develop a patient decision aid (PtDA) following International Patient Decision Aid Standards to help these youth and their families make treatment decisions. DESIGN: Mixed-methods study. SETTING: Brachial plexus clinic in a pediatric tertiary care center. PARTICIPANTS: Five young adults (21-24 years), 14 youth (8-19 years) and their parents, 15 families (children 2-16 years), and 19 clinicians from a brachial plexus clinic participated in the PtDA development. Seventeen other youth (8-18 years) facing treatment decisions regarding their elbow contracture field tested the PtDA prototype. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: In-depth interviews and participant observation to conduct a decisional needs assessment of young adults, youth, parents, and health care professionals involved in these shared decisions. Cognitive interviews to field test the PtDA prototype. RESULTS: Evidence from previously conducted knowledge synthesis and the youth-focused decisional needs assessment qualitative data informed the development of new PtDA prototype, which included a questionnaire-based values clarification method for youth to rate what matters most to them regarding their elbow function, appearance, psychosocial impact, and treatment options. The majority (90%) of youth >11 years who field tested the PtDA prototype understood its content, whereas only 29% of those between 8 and 11 years demonstrated independent comprehension. The majority (69%) responded that they would prefer to use the PtDA on their own either at home or in the clinic waiting room. CONCLUSIONS: This new PtDA can be used to help youth with BPBI and their families to make a personal value-based informed decision regarding treatment options for their elbow flexion contracture.
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Traumatismos del Nacimiento , Plexo Braquial , Contractura , Adolescente , Plexo Braquial/cirugía , Niño , Contractura/etiología , Técnicas de Apoyo para la Decisión , Codo , HumanosRESUMEN
PURPOSE: Hand function outcomes of primary nerve reconstruction for total brachial plexus birth injury (BPBI) are confounded by nerve roots left in continuity, inclusion of secondary procedures, and no assessment of the ability to perform activities of daily living. The purpose of this study was to evaluate the long-term hand function outcomes in a cohort of patients with a complete BPBI who had no nerve root in continuity prior to primary nerve reconstruction targeting the lower trunk. METHODS: This single-center retrospective case series of complete BPBI included patients who underwent primary nerve reconstruction. The outcomes were assessed using the active movement scale (AMS) and brachial plexus outcome measure preoperatively and at the age of 4 and 8 years. RESULTS: Fifty patients with a complete BPBI, of whom 82% (41/50) had an avulsion of C8-T1, underwent primary nerve reconstruction at a mean age of 4.1 months. Compared with the preoperative AMS scores, a statistically significant increase of AMS scores was observed at 4 and 8 years of age for all movements except forearm pronation. Between 4 and 8 years of age, there was a statistically significant improvement of external rotation of the shoulder and elbow flexion as well as diminution of thumb flexion. In the brachial plexus outcome measure assessment, there were 83% (24/29) at 4 years and 81% (21/26) at 8 years who had sufficient functional movement to perform wrist, finger, and thumb activities. CONCLUSIONS: Functional hand outcome was restored to sufficiently perform bimanual activity tasks in 81% (21/26) of patients with a complete BPBI at 8 years of age. This affirmed that primary nerve reconstruction reinnervating the lower trunk can result in a functional extremity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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Traumatismos del Nacimiento , Neuropatías del Plexo Braquial , Plexo Braquial , Transferencia de Nervios , Actividades Cotidianas , Traumatismos del Nacimiento/cirugía , Plexo Braquial/lesiones , Plexo Braquial/cirugía , Neuropatías del Plexo Braquial/cirugía , Niño , Preescolar , Humanos , Lactante , Estudios RetrospectivosRESUMEN
OBJECTIVE: The objective of this study is to elucidate the decision-making experiences of youth with brachial plexus birth injuries who face preference-sensitive decisions regarding treatment options for a persistent elbow contracture. METHODS: Transcripts, research-created drawings, and field notes from in-depth interviews with 5 young adults and 14 youth-parent dyads, and 15 participant observation sessions of families and clinicians in the clinic setting were deductively and inductively coded and thematically analyzed. RESULTS: Youth's shared decision making was influenced by relational processes with their clinicians and parents. Youth's trust in their clinicians' recommendations for pursuing treatment and pressure from their parents to pursue or continue rehabilitation treatment affected how their voices were expressed and heard. Parental emotional adjustment to the birth injury played a role in parental perceptions of what was deemed their youth's best interest in the shared decision. CONCLUSIONS: The decision-making experiences of youth with brachial plexus birth injury illustrate the complexity of paediatric preference-sensitive decisions and the significance of social and emotional factors on these shared decisions. PRACTICE IMPLICATIONS: Opportunity for youth to express their voice without external pressure during shared decision making is needed to make well-informed decisions based on their own values. Interventions such as decision coaching and decision support tools may help youth and parents to formally identify and discuss these relational processes.
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Traumatismos del Nacimiento , Plexo Braquial , Adolescente , Plexo Braquial/lesiones , Niño , Toma de Decisiones , Toma de Decisiones Conjunta , Humanos , Padres , Investigación Cualitativa , Adulto JovenRESUMEN
BACKGROUND: Avulsion of either the C5 or C6 root with intact middle and lower trunks in brachial plexus birth injury is rare. In these cases, only 1 proximal root is available for intraplexal reconstruction. The purpose of the present study was to determine the outcomes of these patients when single-root reconstruction was balanced across the anterior and posterior elements of the upper trunk. METHODS: We performed a retrospective cohort study of prospectively collected data for patients with brachial plexus birth injury who underwent primary nerve reconstruction between 1993 and 2014. Patients were included who had isolated upper-trunk injuries with intact middle and lower trunks. The study group had avulsion of either the C5 or C6 root. The control group had neuroma-in-continuity or ruptures of the upper trunk. Outcomes were assessed with use of the Active Movement Scale and the Brachial Plexus Outcome Measure. The Wilcoxon signed-rank test was utilized to evaluate changes across treatment. RESULTS: Ten patients with brachial plexus birth injury were included in the avulsion cohort. Surgical reconstruction entailed neuroma resection and nerve grafting from the single available root balanced across all distal targets with or without spinal accessory-to-suprascapular nerve transfer. Significant improvements were observed across treatment for both the avulsion and control groups in terms of shoulder abduction, shoulder flexion, external rotation, elbow flexion, and supination. At a mean follow-up of 54.5 ± 8.8 months, patients in the avulsion group achieved Active Movement Scale scores of 6.8 ± 0.4 for elbow flexion and 6.5 ± 0.9 for shoulder flexion and abduction, with lesser recovery observed in external rotation (3.3 ± 2.8). All patients available for Brachial Plexus Outcome Measure assessments demonstrated functional movement. CONCLUSIONS: In the setting of avulsion of 1 upper-trunk root, nerve reconstruction by grafting of the upper trunk from the other upper-trunk root provides improved movement, high Active Movement Scale scores, and satisfactory function according to the Brachial Plexus Outcome Measure. These data provide support for a strategy that ensures the entire upper trunk is adequately reconstructed in the setting of upper-trunk lesions. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Traumatismos del Nacimiento/cirugía , Neuropatías del Plexo Braquial/cirugía , Plexo Braquial/lesiones , Transferencia de Nervios/métodos , Nervios Espinales/lesiones , Traumatismos del Nacimiento/fisiopatología , Neuropatías del Plexo Braquial/etiología , Neuropatías del Plexo Braquial/fisiopatología , Vértebras Cervicales , Articulación del Codo/inervación , Articulación del Codo/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Rango del Movimiento Articular , Estudios Retrospectivos , Articulación del Hombro/inervación , Articulación del Hombro/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Avulsion of either the C5 or C6 root with intact middle and lower trunks in brachial plexus birth injury is rare. In these cases, only 1 proximal root is available for intraplexal reconstruction. The purpose of the present study was to determine the outcomes of these patients when single-root reconstruction was balanced across the anterior and posterior elements of the upper trunk. METHODS: We performed a retrospective cohort study of prospectively collected data for patients with brachial plexus birth injury who underwent primary nerve reconstruction between 1993 and 2014. Patients were included who had isolated upper-trunk injuries with intact middle and lower trunks. The study group had avulsion of either the C5 or C6 root. The control group had neuroma-in-continuity or ruptures of the upper trunk. Outcomes were assessed with use of the Active Movement Scale and the Brachial Plexus Outcome Measure. The Wilcoxon signed-rank test was utilized to evaluate changes across treatment. RESULTS: Ten patients with brachial plexus birth injury were included in the avulsion cohort. Surgical reconstruction entailed neuroma resection and nerve grafting from the single available root balanced across all distal targets with or without spinal accessory-to-suprascapular nerve transfer. Significant improvements were observed across treatment for both the avulsion and control groups in terms of shoulder abduction, shoulder flexion, external rotation, elbow flexion, and supination. At a mean follow-up of 54.5 ± 8.8 months, patients in the avulsion group achieved Active Movement Scale scores of 6.8 ± 0.4 for elbow flexion and 6.5 ± 0.9 for shoulder flexion and abduction, with lesser recovery observed in external rotation (3.3 ± 2.8). All patients available for Brachial Plexus Outcome Measure assessments demonstrated functional movement. CONCLUSIONS: In the setting of avulsion of 1 upper-trunk root, nerve reconstruction by grafting of the upper trunk from the other upper-trunk root provides improved movement, high Active Movement Scale scores, and satisfactory function according to the Brachial Plexus Outcome Measure. These data provide support for a strategy that ensures the entire upper trunk is adequately reconstructed in the setting of upper-trunk lesions. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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With the advent of highly sensitive technologies such as tandem mass spectrometry and next-generation sequencing, recombinant antibodies are now routinely analyzed for the presence of low-level sequence variants including amino acid misincorporations. During mAb cell culture process development, we found that proline was replaced with the non-canonical amino acid, hydroxyproline, in the protein sequence. We investigated the relationship between proline content in the cell culture media and proline sequence variants and found that the proline concentration was inversely correlated with the amount of sequence variants detected in the protein sequence. Hydroxyproline incorporation has been previously reported in recombinant proteins produced in mammalian expression systems as a post-translational modification. Given the dependency on proline levels, the mechanism was then investigated. To address the possibility of co-translational misincorporation of hydroxyproline, we used tandem mass spectrometry to measure incorporation of stable-isotope labelled hydroxyproline added to the feed of a production bioreactor. We discovered co-translational misincorporation of labelled hydroxyproline in the recombinant antibody. These findings are significant, since they underscore the need to track non-canonical amino acid incorporation as a co-translational event in CHO cells. Understanding the mechanism of hydroxyproline incorporation is crucial in developing an appropriate control strategy during biologics production.
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Anticuerpos Monoclonales/biosíntesis , Reactores Biológicos , Hidroxiprolina/metabolismo , Procesamiento Proteico-Postraduccional , Animales , Anticuerpos Monoclonales/genética , Células CHO , Cricetulus , Hidroxiprolina/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genéticaRESUMEN
The bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. To ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. Regulatory agencies and the biotechnology industry consider cell line "clonal origin" an important aspect of maintaining process control. Demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few years, and the industry has improved methods and devised standards to increase the probability and/or assurance of clonal derivation. However, older production cell lines developed before the implementation of these methods, herein referred to as "legacy cell lines," may not meet current regulatory expectations for demonstration of clonal derivation. In this article, the members of the IQ Consortium Working Group on Clonality present our position that the demonstration of process consistency and product comparability of critical quality attributes throughout the development life cycle should be sufficient to approve a license application without additional genetic analysis to support clonal origin, even for legacy cell lines that may not meet current day clonal derivation standards. With this commentary, we discuss advantages and limitations of genetic testing methods to support clonal derivation of legacy cell lines and wish to promote a mutual understanding with the regulatory authorities regarding their optional use during early drug development, subsequent to Investigational New Drug (IND) application and before demonstration of product and process consistency at Biologics License Applications (BLA) submission.
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Productos Biológicos/síntesis química , Productos Biológicos/farmacología , Desarrollo de Medicamentos/métodos , Pruebas Genéticas/métodos , Secuenciación Completa del Genoma/métodos , Animales , Células CHO , Línea Celular , Cricetinae , Cricetulus , Desarrollo de Medicamentos/normas , Pruebas Genéticas/normas , Desarrollo de Programa/métodos , Desarrollo de Programa/normas , Secuenciación Completa del Genoma/normasRESUMEN
PURPOSE: To synthesize the evidence on the prevalence and etiology of elbow flexion contractures secondary to brachial plexus birth injury (BPBI). METHODS: Using Arksey and O'Malley's scoping review framework, MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched, followed by a comprehensive grey literature search. Articles and abstracts of studies of all level of evidence on the prevalence, natural history, clinical presentation, etiology, and treatment of elbow flexion contractures in BPBI were included. RESULTS: Of the 884 records found, 130 full text articles were reviewed, and 57 records were included. The median prevalence of elbow flexion contracture in BPBI was 48%. The magnitude of the contractures was between 5 and 90 degrees. Contractures > 30 degrees were found in 21% to 36% of children. With recent clinical and lab studies, there is stronger evidence that the contractures are largely due to the effects of denervation causing failure in the growth of the affected flexor muscles, while muscle imbalance, splint positioning, and postural preferences play a smaller role. CONCLUSION: The etiology of elbow flexion contractures is multifaceted. The contribution of growth impairment in the affected muscles offers greater understanding as to why maintaining passive range of motion in these contractures can be difficult.
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Contractura , Codo , Parálisis Neonatal del Plexo Braquial/complicaciones , Adolescente , Niño , Contractura/epidemiología , Contractura/etiología , Contractura/rehabilitación , Humanos , PrevalenciaRESUMEN
PURPOSE: To conduct a systematic review of studies on non-surgical and surgical interventions for elbow flexion contractures secondary to brachial plexus birth injury (BPBI). METHODS: MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched for randomized controlled trials, observational studies, and case series studies on treatment of elbow flexion contractures secondary to BPBI. Study quality was evaluated using the Effective Public Health Practice Project tool. RESULTS: Of the 950 records found, 132 full text articles were reviewed, and 3 cohort studies and 8 case series were included. The overall methodological quality of included studies was weak. The weak quality evidence demonstrated that significant gains in elbow extension passive range of motion (ROM) can be achieved with serial casting (range: 15 to 34.5 degrees) or elbow release surgery (range: 28.4 to 30.0 degrees). At best, a reduction to an elbow contracture between -15.0 and -18.8 degrees (casting) and -8.0 and -43.6 (elbow release surgery) can be achieved. Insufficient outcomes on elbow flexion ROM and strength were found in both non-surgical and surgical studies. CONCLUSION: The quality of evidence on the effectiveness of interventions for an elbow flexion contracture secondary to BPBI is weak. In the context of insufficient evidence on the risks of pursuing such interventions, it is prudent to attempt non-surgical interventions prior to surgery. LEVEL OF EVIDENCE: III - systematic review of level IV studies.
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Tratamiento Conservador/métodos , Contractura , Codo , Parálisis Neonatal del Plexo Braquial/complicaciones , Procedimientos Ortopédicos/métodos , Contractura/etiología , Contractura/rehabilitación , Contractura/terapia , Humanos , Resultado del TratamientoRESUMEN
PURPOSE: Studies are limited on sensory outcome in children with brachial plexus birth injury (BPBI). The purpose of this research was to evaluate the sensory function of the hand in children with BPBI who had microsurgical reconstruction of the brachial plexus. METHODS: The sensory thresholds of children with upper and total plexus injury were evaluated with the Weinstein Enhanced Sensory Test and a test of stereognosis. RESULTS: A total of 63 children participated (aged 10.92 ± 3.29 years), 24 (38%) of whom had abnormal sensory thresholds in the affected hand. Only 4 children had loss of protective sensation or higher thresholds. These 4 measurements were all identified in the territory of the superficial branch of the radial nerve. Twelve children with upper plexus (43%) and 12 (34%) with total plexus injury had sensory impairment in the affected hand. These proportions were not statistically different. Of all children evaluated, 18 (29%) had a lower stereognosis score in the affected hand compared with the unaffected hand. The proportions of children with impairment in stereognosis in the upper plexus group (n = 5; 18%) versus the total plexus group (n = 13; 37%) were not statistically different. Age at the time of assessment, sex, upper versus total plexus injury, number of root avulsions, subjective report of altered sensation, and Faces Pain Scale-Revised score were not related to sensory impairment in the affected hand. CONCLUSIONS: Sensory recovery in BPBI after microsurgical reconstruction in children with total plexus injury who had reconstruction of the lower trunk had the potential to achieve sensory recovery similar to their upper plexus counterparts. A large proportion of children achieve normal sensory outcome, and those who had deficits had mild impairments. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.
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Neuropatías del Plexo Braquial/cirugía , Plexo Braquial/cirugía , Recuperación de la Función/fisiología , Umbral Sensorial/fisiología , Adolescente , Traumatismos del Nacimiento/fisiopatología , Traumatismos del Nacimiento/cirugía , Plexo Braquial/lesiones , Plexo Braquial/fisiopatología , Neuropatías del Plexo Braquial/fisiopatología , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Microcirugia , Examen NeurológicoRESUMEN
Purpose: The purpose of this study was to identify the functional and aesthetic factors associated with an elbow flexion contracture in children with a brachial plexus birth injury who identified their elbow flexion contracture as a problem. Materials and methods: A retrospective cross-sectional study of children with brachial plexus birth injury between 7 and 18 years was conducted to compare the characteristics of children who had treatment for an elbow flexion contracture with those who did not. Results: Fifty of the 200 children included in the study had treatment (one surgical release, 49 serial casting/splinting) for the elbow flexion contracture. Children who had treatment were an average 12.4 years of age, which was significantly older than those who did not have treatment. Elbow extension passive range of motion was an average -40.6° prior to treatment. Stepwise logistical regression model indicated that children who had treatment had greater severity in elbow contracture, higher Brachial Plexus Outcome Measure Activity scores, and lower Brachial Plexus Outcome Measure Self-Evaluation Appearance scores. Conclusions: In addition to severity of contracture and function, perceived appearance of the limb is important factor to evaluate in the management of elbow flexion contractures. Implications for rehabilitation Priority is often given to evaluate the functional implications of elbow flexion contractures in brachial plexus birth injury to determine recommendations for rehabilitation interventions such as serial casting and splinting. Findings in this study indicate that severity of contracture, upper extremity activity function, and perceived upper extremity appearance are important factors in the management of elbow contractures. In addition to upper extremity function, routine evaluation of perceived upper extremity appearance in children and adolescents is important in the management of elbow flexion contractures.