Multidisciplinary neurofibromatosis conference in the management of patients with neurofibromatosis type 1 and schwannomatosis in a single tertiary care institution.

OBJECTIVE: To evaluate the role of weekly neurofibromatosis (NF) multi-disciplinary conferences (MDC) on the diagnostic and therapeutic plan for patients with NF type 1 (NF1) and schwannomatosis (SWN). MATERIALS AND METHODS: This retrospective study reviewed patients with confirmed or suspected NF1 and SWN discussed in weekly MDC from March to July 2021. Demographic data collected included patient age, sex, pre-conference and post-conference diagnosis, radiological studies reviewed, and provider specialties in attendance. Outcomes reported included changes in imaging interpretation and treatment plans, changes in post-conference diagnosis relative to pre-conference diagnosis, and time to completion of the recommended change in treatment. RESULTS: Data from 17 MDC "pre-conference" lists included 75 patients (38 female, 37 males, mean age (years): 38 (range: 6-80)) with NF1 (52%, 39/75) and SWN (36%, 27/75) discussed over a total of 91 case reviews. 18.7% (14/75) of all patients had NF2-related SWN, and 17.3% (13/75) of all patients had non-NF2 SWN. The MDC led to changes in imaging interpretation in 18.7% and changes in patient management in 74.7% (diagnostic testing (n = 52), surgical plan (n = 24), medical treatment (n = 9), clinical trial status (n = 4), and radiation treatment (n = 1)) of cases. Among patients for whom a change in management was recorded, 91% (62/68) completed at least one recommendation (mean time to completion (days): 41.4 (range: 0-278)). CONCLUSION: Weekly MDC changes the diagnostic and therapeutic management of the majority of patients discussed (74.7%) and promotes a high adherence rate to recommendations (91%).

Understanding barriers to diagnosis in a rare, genetic disease: Delays and errors in diagnosing schwannomatosis.

Diagnosis of rare, genetic diseases is challenging, but conceptual frameworks of the diagnostic process can guide quality improvement initiatives. Using the National Academy of Medicine diagnostic framework, we assessed the extent of, and reasons for diagnostic delays and diagnostic errors in schwannomatosis, a neurogenetic syndrome characterized by nerve sheath tumors and chronic pain. We reviewed the medical records of 97 people with confirmed or probable schwannomatosis seen in two US tertiary care clinics. Time-to-event analysis revealed a median time from first symptom to diagnosis of 16.7 years (95% CI, 7.5-26.0 years) and median time from first medical consultation to diagnosis of 9.8 years (95% CI, 3.5-16.2 years). Factors associated with longer times to diagnosis included initial signs/symptoms that were intermittent, non-specific, or occurred at younger ages (p < 0.05). Thirty-six percent of patients were misdiagnosed; misdiagnoses were of underlying genetic condition (18.6%), pain etiology (16.5%), and nerve sheath tumor presence/pathology (11.3%) (non-mutually exclusive categories). One-fifth (19.6%) of patients had a clear missed opportunity for genetics workup that could have led to an earlier schwannomatosis diagnosis. These results suggest that interventions in clinician education, genetic testing availability, expert review of pathology findings, and automatic triggers for genetics referrals may improve diagnosis of schwannomatosis.

The Natural History of Non-operatively Managed Legg-Calvé-Perthes' Disease.

Background: The purpose of this study was to examine the evolution of Legg-Calvé-Perthes' disease (LCPD) among children from British Columbia (BC), Canada who were treated non-operatively and to compare the results to a previously conducted study in India. Methods: This was a retrospective review of patients treated non-operatively for LCPD in BC between 1990 and 2006 compared with a cohort from India. Demographic and treatment information were collected from medical records. Radiographs were assigned modified Waldenstrom, Catterall, Salter-Thompson and Herring classifications and intra- and interobserver reliability were assessed. We evaluated epiphyseal extrusion (EE) and metaphyseal width (MW), and assessed radiographs using the Mose and modified Stulberg classifications. Results: 102 hips (90 patients) had radiographs available for evaluation. 95% of the BC cohort presented as Waldenstrom stages I and II, whereas, 90% of the Indian cohort presented as IIIa. Final EE was similar for both groups (BC 26.8%, India 27.3%) and final MW was 119% in both groups. Modified Waldenstrom and Herring classifications had substantial intra- and interobserver reliability, while Salter-Thompson and Catterall classifications had moderate agreement at best. Most hips were Catterall IV (80%) and Herring C (89%) for the BC cohort compared to only 44% and 43% of Indian hips, respectively. Most hips were irregular according to the Mose classification (BC 43%, India 52%) and aspherical according to the Stulberg classification (BC 78%). Conclusions: We found similar radiographic progression and final radiographic appearances of LCPD in India and BC though differences in the distribution of the classification systems warrant further study. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-021-00543-x.

A clinically and genomically annotated nerve sheath tumor biospecimen repository.

Nerve sheath tumors occur as a heterogeneous group of neoplasms in patients with neurofibromatosis type 1 (NF1). The malignant form represents the most common cause of death in people with NF1, and even when benign, these tumors can result in significant disfigurement, neurologic dysfunction, and a range of profound symptoms. Lack of human tissue across the peripheral nerve tumors common in NF1 has been a major limitation in the development of new therapies. To address this unmet need, we have created an annotated collection of patient tumor samples, patient-derived cell lines, and patient-derived xenografts, and carried out high-throughput genomic and transcriptomic characterization to serve as a resource for further biologic and preclinical therapeutic studies. In this work, we release genomic and transcriptomic datasets comprised of 55 tumor samples derived from 23 individuals, complete with clinical annotation. All data are publicly available through the NF Data Portal and at http://synapse.org/jhubiobank.

Association between patient-reported outcomes and objective disease indices in people with NF2.

OBJECTIVE: The association between patient-reported outcomes and currently used clinical trial endpoints, including total vestibular schwannoma (VS) volume and word recognition score (WRS) in neurofibromatosis type 2 (NF2), is not known. METHODS: A prospective observational study enrolling adult patients with NF2 was conducted at a single specialty center. Measures included: NF2 impact on quality of life (NFTI-QOL), short form (SF)-36; total VS volume, WRS; provider- and patient-reported disease severity (ProvSev, PatSev) measured with an institutionally derived multi-item (e.g., symptom burden, age-of-onset, and fatality-risk) and single-item Likert (mild, moderate, severe) scale. RESULTS: Fifty-one patients were enrolled between June 2014 and August 2017. Mean age was 42.1 ± 18.2 years and 37.3% patients were male. Mean WRS was 74.4 ± 37.3%; mean total VS volume was 4.2 ± 5.2 cc. Additional lesions were common including meningioma (79.2%) and spinal ependymoma (39.6%). Mean NFTI-QOL score was 7.6 ± 4.9 and correlated with responses on the SF-36. NFTI-QOL also correlated well with PatSev (r = 0.63, p < 0.001) and both multi- and single-item ProvSev (r = 0.62, p < 0.001; r = 0.52, p < 0.001, respectively). A weak correlation was observed between NFTI-QOL and WRS (r = -0.34, p = 0.0156). There was no correlation with VS volume (r = 0.23, p = 0.15). CONCLUSIONS: The NFTI-QOL correlated well with multiple measures of disease severity but not commonly accepted endpoints for NF2 clinical trials including total VS volume in this US cohort of patients with NF2. This suggests that the NFTI-QOL captures components of the patient experience not sufficiently represented by objective measures of disease and underscores the important and complementary role of patient-focused measures in therapeutic outcome assessment in people with NF2.

No benefit to surgical fixation of flail chest injuries compared with modern comprehensive management: results of a retrospective cohort study.

BACKGROUND: Chest wall trauma is a common cause of morbidity and mortality. Recent technological advances and scientific publications have created a renewed interest in surgical fixation of flail chest. However, definitive data supporting surgical fixation are lacking, and its virtues have not been evaluated against modern, comprehensive management protocols. METHODS: Consecutive patients undergoing rib fracture fixation with rib-specific locking plates at 2 regional trauma centres between July 2010 and August 2012 were matched to historical controls with similar injury patterns and severity who were managed nonoperatively with modern, multidisciplinary protocols. We compared short- and long-term outcomes between these cohorts. RESULTS: Our patient cohorts were well matched for age, sex, injury severity scores and abbreviated injury scores. The nonoperatively managed group had significantly better outcomes than the surgical group in terms of ventilator days (3.1 v. 6.1, p = 0.012), length of stay in the intensive care unit (3.7 v. 7.4 d, p = 0.009), total hospital length of stay (16.0 v. 21.9 d, p = 0.044) and rates of pneumonia (22% v. 63%, p = 0.004). There were no significant differences in long-term outcomes, such as chest pain or dyspnea. CONCLUSION: Although considerable enthusiasm surrounds surgical fixation of flail chest injuries, our analysis does not immediately validate its universal implementation, but rather encourages the use of modern, multidisciplinary, nonoperative strategies. The role of rib fracture fixation in the modern era of chest wall trauma management should ultimately be defined by prospective, randomized trials.

CONTEXTE: Les traumatismes à la paroi thoracique sont une cause courante de morbidité et de mortalité. Dernièrement, des avancées technologiques et des articles scientifiques ont ravivé l'intérêt à l'égard du traitement chirurgical du volet costal. Les données fiables appuyant la fixation chirurgicale sont toutefois rares, et les avantages de cette technique n'ont pas été comparés à ceux de protocoles de prise en charge complets et modernes. MÉTHODES: Nous avons jumelé des patients consécutifs admis dans 2 centres régionaux de traumatologie entre juillet 2010 et août 2012 pour une fixation d'une fracture des côtes à l'aide de plaques verrouillées avec un groupe témoin rétrospectif présentant des blessures de type et de gravité semblables, toutefois pris en charge selon des protocoles multidisciplinaires modernes ne nécessitant aucune intervention chirurgicale. Nous avons ensuite comparé les issues à court et à long terme dans ces cohortes. RÉSULTATS: Les cohortes étaient bien appariées sur le plan de l'âge, du sexe et des indices de gravité des blessures. Les résultats des patients n'ayant pas subi d'intervention chirurgicale étaient significativement meilleurs que ceux de l'autre groupe en ce qui concerne le nombre de jours sous ventilation assistée (3,1 c. 6,1; p = 0,012), la durée du séjour aux soins intensifs (3,7 c. 7,4 jours; p = 0,009), la durée totale du séjour à l'hôpital (16,0 c. 21,9 jours; p = 0,044) et le taux de pneumonie (22 % c. 63 %; p = 0,004). Aucune différence significative n'a été observée en ce qui concerne les répercussions à long terme telles que les douleurs thoraciques ou la dyspnée. CONCLUSION: Si la fixation chirurgicale des blessures au volet costal suscite un grand enthousiasme, les résultats de notre analyse n'appuient pas le recours systématique à cette intervention, mais encouragent plutôt l'utilisation de stratégies modernes multidisciplinaires sans intervention chirurgicale. En conclusion, le rôle de la fixation des fractures des côtes dans la prise en charge moderne des traumatismes à la paroi thoracique devrait être défini dans le cadre d'études prospectives randomisées.

Citation classics in pediatric orthopaedics.

BACKGROUND: The purpose of this study was to identify the clinical pediatric orthopaedic articles with at least 100 citations published in all orthopaedic journals and to examine their characteristics. METHODS: All journals dedicated to orthopaedics and its subspecialties were selected from the Journal Citation Report 2001 under the subject category "orthopedics." Articles cited 100 times or more were identified using the database of the Science Citation Index Expanded (SCI-EXPANDED, 1900 to present). The articles were ranked in a comprehensive list. Two authors independently reviewed the full text of each article and applied the inclusion and exclusion criteria to the list of articles. The 2 lists were then compared. All disagreements were resolved by consensus with input from the senior author. The final list of pediatric orthopaedic articles was then compiled. RESULTS: There were a total of 49 journals under the search category "orthopedics." Five journals were excluded as they were non-English journals. The remaining 44 journals were screened for articles with at least 100 citations. A total of 135 clinical pediatric orthopaedic articles cited at least 100 times were included. The most cited article was cited 692 times. The mean number of citations per article was 159 (95% confidence interval, 145-173). All the articles were published between 1949 and 2001, with 1980 and 1989 producing the most citation classics (34). The majority (90) originated from the United States, followed by the United Kingdom (12) and Canada (11). Scoliosis/kyphosis was the most common topic with 26 papers. The second most common subject was hip disorders (24). Therapeutic studies were the most common study type (71). Ninety-seven papers were assigned a 4 for level of evidence. CONCLUSIONS: The list of citation classics in pediatric orthopaedic articles is useful for several reasons. It identifies important contributions to the field of pediatric orthopaedics and their originators; it facilitates the understanding and discourse of modern pediatric orthopaedic history and reveals trends in pediatric orthopaedics.

Is larger scoliosis curve magnitude associated with increased perioperative health-care resource utilization?: a multicenter analysis of 325 adolescent idiopathic scoliosis curves.

BACKGROUND: The treatment of patients with large adolescent idiopathic scoliosis curves has been associated with increased surgical complexity. The purpose of this study was to determine whether surgical correction of larger adolescent idiopathic scoliosis curves increased the utilization of health-care resources and to identify potential predictors associated with increased perioperative health-care resource utilization. METHODS: A nested cohort of patients with adolescent idiopathic scoliosis with Lenke type 1A and 1B curves were identified from a prospective longitudinal multicenter database. Four perioperative outcomes were selected as the primary health-care resource utilization outcomes of interest: operative time, number of vertebral levels instrumented, duration of hospitalization, and allogeneic blood transfusion. The effect of curve magnitude on these outcomes was assessed with use of univariate and multivariate regression. RESULTS: Three hundred and twenty-five patients with a mean age of 15 ± 2 years were included. The mean main thoracic curve was 54.4° ± 7.8°. Larger curves were associated with longer operative time (p = 0.03), a greater number of vertebral levels instrumented (p = 0.0005), and the need for blood transfusion (with every 10° increase associated with 1.5 times higher odds of receiving a transfusion). In addition to curve magnitude, surgical center, bone graft method, and upper and lower instrumented levels were strong predictors of operative time (R2 = 0.76). The duration of hospitalization was influenced by the surgical center and intraoperative blood loss (R2 < 0.4), whereas the number of levels instrumented was influenced by the curve magnitude, curve correction percentage, upper instrumented vertebra, and surgical center (R2 = 0.64). CONCLUSIONS: Correction of larger curves was associated with increased utilization of perioperative health-care resources, specifically longer operative time, a greater number of vertebral levels instrumented, and higher odds of receiving a blood transfusion.

Recurrent viral-induced compartment syndrome.

UNLABELLED: Rhabdomyolysis and compartment syndrome are rare but a limb-threatening complication of viral myositis. Because of the potential for severe consequences of compartment syndrome, clinicians should maintain a high index of suspicion when examining children with rhabdomyolysis due to viral myositis. We report a case of recurrent bilateral thigh compartment syndrome in a patient with influenza A, subtype pandemic H1N1-2009. CASE: An 8-year-old girl with a history of rhabdomyolysis, acute renal failure, and compartment syndrome secondary to parainfluenza infection that resulted in release of her lower limb compartments presented with a 3-day history of flu symptoms and increasing bilateral thigh pain. Compartment syndrome was confirmed by intracompartmental pressure measurements and comparison of intracompartmental pressure measurements to diastolic blood pressure. The compartments were released. She also experienced acute renal failure, which was treated by continuous renal replacement therapy and hemodialysis. At her most recent orthopedic follow-up, she was doing well. CONCLUSIONS: This is the first reported case of recurrent rhabdomyolysis and compartment syndrome as a complication of viral myositis. This case highlights the importance of maintaining a high index of suspicion for compartment syndrome in the child with viral myositis.

The epidemiology of nonaccidental trauma in children.

BACKGROUND: Abuse of children is abhorrent in Western society and, yet, is not uncommon. Nonaccidental trauma (NAT) is the result of a complex sociopathology. Not all of the causative factors of NAT are known, many are incompletely described, not all function in each case, and many are secondary to preexisting pathology in other areas. QUESTIONS/PURPOSES: We therefore addressed the following questions in this review: (1) what is the general incidence of NAT; (2) what factors are intrinsic to the abused child, family, and society; and (3) what orthopaedic injuries are common in NAT? METHODS: We searched Medline, Medline In Process & Other Non-Indexed Citations, and Embase using OVID. Only one article fit our inclusion criteria; therefore, this is a descriptive generalized review of the epidemiology of NAT. RESULTS: The general incidence of NAT ranges from 0.47 per 100,000 to 2000 per 100,000. Younger children are at greater risk of NAT than older children. Parents are often the perpetrators of the abuse. Rib fractures are highly indicative of NAT in young children. CONCLUSIONS: It is important to consider child, family, and societal factors when confronted with suspicions of child abuse. Our review demonstrates the currently limited information on the true incidence of NAT. To determine a much more accurate incidence of NAT, there needs to be a population-based surveillance program conducted through primary care providers.

Iatrogenic ulnar nerve injury after the surgical treatment of displaced supracondylar fractures of the humerus: number needed to harm, a systematic review.

BACKGROUND: Supracondylar fractures of the humerus are common pediatric elbow injuries. Most displaced or angulated fractures are treated by closed reduction and percutaneous pinning, with either a crossed pin or lateral pin configuration. The purpose of this study was to conduct a systematic review to determine if there is an increased risk of iatrogenic nerve injury associated with the crossed pin configuration. METHODS: Relevant articles were identified by searching electronic databases and hand searching-related journal and conference proceedings. Within each trial, the risk of iatrogenic ulnar nerve injury was calculated for each pinning technique. For studies comparing crossed versus lateral pinning, the resulting trial-based differences in risk estimates were pooled using a random effects meta-analysis. A number needed to harm was determined using the pooled risk difference. RESULTS: Thirty-two trials consisting of 2639 patients were used in the pooled analysis. The pooled risk difference of iatrogenic ulnar nerve injury is 0.035 (95% confidence interval, 0.014-0.056), with a higher incidence of injury in the crossed pinning group. The weighed number needed to harm for the crossed pinning is 28 (95% confidence interval, 17-71). CONCLUSIONS: The results of this review suggest that there is an iatrogenic ulnar nerve injury for every 28 patients treated with the crossed pinning compared with the lateral pinning. Further research is necessary to ensure that the optimal pinning technique is chosen to treat these factors. LEVEL OF EVIDENCE: Level III.

The effect of surgical timing on operative duration and quality of reduction in Type III supracondylar humeral fractures in children.

PURPOSE: To determine the influence of the time from injury to surgery of Type III supracondylar fractures on operative duration and quality of reduction. METHODS: A retrospective review of Type III supracondylar fractures treated by closed reduction and percutaneous pinning over a 3-year period was performed. RESULTS: The subjects were divided into two groups based on the time from injury to surgery (IST): Group 1 (<8 h) 48 subjects and Group 2 (>8 h) 39 subjects. There was no difference in the mean age or gender ratio between the two groups. There were no cases of compartment syndrome or conversion to open reduction in either group. The mean IST was 669 min. The mean IST for Group 1 was 340 min and it was 1,074 min for Group 2. The operative duration for Group 1 was 32.56 min and for Group 2 it was 31.72 min (P = 0.77). There were no significant differences in the quality of reduction. CONCLUSIONS: There was no difference in the operative duration demonstrated between IST <8 h and IST >8 h. This failure to demonstrate a difference should not be interpreted as demonstrating equivalence. This study does not conclude that all displaced supracondylar fractures should be delayed, though it does inform the surgeon that, if compelled to delay surgery, this series did not demonstrate an increased risk of complications, nor a worsened quality of reduction.

MEDLINE, EMBASE, and Cochrane index most primary studies but not abstracts included in orthopedic meta-analyses.

OBJECTIVE: To test the hypothesis that all primary studies used in orthopedic meta-analyses are indexed in MEDLINE or EMBASE. STUDY DESIGN AND SETTING: Using MEDLINE from 1995 to 2005, we retrieved all published meta-analyses of orthopedic surgical interventions. The primary studies in each meta-analysis were defined as the "gold standard" set. MEDLINE and EMBASE were searched for each primary study, and a recall rate was calculated. Secondary searches were performed using Web of Science (WoS), the Cochrane databases, and CINAHL. RESULTS: High recall rates were achieved searching MEDLINE (90%) and EMBASE (81%) for the gold standard set, and the combined search retrieved 91%. Titles not indexed by MEDLINE or EMBASE included 45 abstracts, eight journal articles, and three unpublished studies. Searching the Cochrane databases yielded 36 titles not in MEDLINE or EMBASE. Using all three databases produced 97% recall of the primary studies; WoS and CINAHL did not increase the recall rate. CONCLUSIONS: These results suggest that a very high percentage of primary research in orthopedics can be found using the major databases. Additional database searches are unlikely to increase the yield of published manuscripts; however, conference proceedings and journal supplements should still be searched to ensure that relevant remaining reports are identified.

The segway personal transporter as an alternative mobility device for people with disabilities: a pilot study.

OBJECTIVES: To determine the functional measures that best correlate with the skill levels of people with disabilities who operate a Segway Personal Transporter, and-using a qualitative analysis-to explore subjects' experience with the Segway. DESIGN: A prospective study encompassing 3 training sessions with the Segway to correlate subjects' functional ability (eg, cognition, balance, mobility, muscle strength) with their skill level on the device. SETTING: A provincial adult rehabilitation center. PARTICIPANTS: Twenty-three subjects (age range, 19-65y) with a wide range of disabilities (eg, multiple sclerosis, spinal cord injury, amputation) who could walk at least 6m with or without assistance. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Segway Task Assessment, Berg Balance Scale, and Timed Up & Go test. RESULTS: No correlation was found because all participants successfully completed the final Segway Task Assessment, regardless of scores on functional assessments. CONCLUSIONS: The Segway is a useful device for a broad range of populations with functional disabilities. Subjects found the Segway easy to use and were excited about its potential as an assistive device for use in their communities.

A quality assessment of randomized clinical trials in pediatric orthopaedics.

The promotion and practice of evidence-based medicine necessitates a critical evaluation of medical literature, including the criterion standard of randomized clinical trials (RCTs). Recent studies have examined the quality of RCTs in various surgical specialties, but no study has focused on pediatric orthopaedics. The purpose of this study was to assess and describe the quality of RCTs published in the last 10 years in journals with high clinical impact in pediatric orthopaedics. All of the RCTs in pediatric orthopaedics published in 5 well-recognized journals between 1995 and 2005 were reviewed using the Detsky Quality Assessment Scale. The mean percentage score on the Detsky scale was 53% (95% confidence interval, 46%-60%). Only 7 (19%) of the articles satisfied the threshold for a satisfactory level of methodological quality (Detsky >75%). Most RCTs in pediatric orthopaedics that are published in well-recognized peer-reviewed journals demonstrate substantial deficiencies in methodological quality. Particular areas of weakness include inadequate rigor and reporting of randomization methods, use of inappropriate or poorly described outcome measures, inadequate description of inclusion and exclusion criteria, and inappropriate statistical analysis. Further efforts are necessary to improve the conduct and reporting of clinical trials in this field to avoid inadvertent misinformation of the clinical community.