Publications

PURPOSE: Multiple FGFR inhibitors are currently in clinical trials enrolling adults with different solid tumors, while very few enroll pediatric patients. We determined the types and frequency of FGFR alterations (FGFR1-4) in pediatric cancers to inform future clinical trial design.

METHODS: Tumors with FGFR alterations were identified from two large cohorts of pediatric solid tumors subjected to targeted DNA sequencing: The Dana-Farber/Boston Children's Profile Study (n = 888) and the multi-institution GAIN/iCAT2 (Genomic Assessment Improves Novel Therapy) Study (n = 571). Data from the combined patient population of 1,395 cases (64 patients were enrolled in both studies) were reviewed and cases in which an FGFR alteration was identified by OncoPanel sequencing were further assessed.

RESULTS: We identified 41 patients with tumors harboring an oncogenic FGFR alteration. Median age at diagnosis was 8 years (range, 6 months-26 years). Diagnoses included 11 rhabdomyosarcomas, nine low-grade gliomas, and 17 other tumor types. Alterations included gain-of-function sequence variants (n = 19), amplifications (n = 10), oncogenic fusions (FGFR3::TACC3 [n = 3], FGFR1::TACC1 [n = 1], FGFR1::EBF2 [n = 1], FGFR1::CLIP2 [n = 1], and FGFR2::CTNNA3 [n = 1]), pathogenic-leaning variants of uncertain significance (n = 4), and amplification in combination with a pathogenic-leaning variant of uncertain significance (n = 1). Two novel FGFR1 fusions in two different patients were identified in this cohort, one of whom showed a response to an FGFR inhibitor.

CONCLUSION: In summary, activating FGFR alterations were found in approximately 3% (41/1,395) of pediatric solid tumors, identifying a population of children with cancer who may be eligible and good candidates for trials evaluating FGFR-targeted therapy. Importantly, the genomic and clinical data from this study can help inform drug development in accordance with the Research to Accelerate Cures and Equity for Children Act.

Burn wounds result from exposure to hot liquids, chemicals, fire, electric discharge or radiation. Wound severity ranges from first-degree injury, which is superficial, to fourth-degree injury, which exposes bone, tendons and muscles. Rapid assessment of burn depth and accurate wound management in the outpatient setting is critical to prevent injury progression into deeper layers of the dermis. Injury progression is of particular pertinence to second-degree burns, which are the most common form of thermal burn. As our understanding of wound healing advances, treatment options and technologies for second-degree burn management also evolve. Polymeric hydrogels are a class of burn wound dressings that adhere to tissue, absorb wound exudate, protect from the environment, can be transparent facilitating serial wound evaluation and, in some cases, enable facile removal for dressing changes. This review briefly describes the burn level classification and common, commercially available dressings used to treat second-degree burns, and then focuses on new polymeric hydrogel burn dressings under preclinical development analyzing their design, structure and performance. The review presents the follow key learning points: (1) introduction to the integument system and the wound-healing process; (2) classification of burns according to severity and clinical appearance; (3) available dressings currently used for second-degree burns; (4) introduction to hydrogels and their preparation and characterization techniques; and (5) pre-clinical hydrogel burn wound dressings currently being developed.

Background: Management of distal radius fractures in patients over 65 is a topic of significant study, but there are variations within this group in terms of independence and activity level. This study compares the outcomes of operative distal radius fracture treatment in patients over 75 with those aged 65 to 74, to evaluate the effects of patient demand and advanced age on outcome. Methods: A retrospective review of a single-institution distal radius fracture database was performed. All patients over age 65 were evaluated for inclusion. Patient factors including activity, independence level, and quick disabilities of the arm, shoulder and hand (QuickDASH) score were recorded. Patients were selected for open reduction and internal fixation (ORIF) based on a discussion between the patient and the treating surgeon. Outcome measures including QuickDASH were recorded at 1-year post-injury. Patients aged 65 to 74 and 75 and over were compared to evaluate for demographic, functional, and outcome differences. Results: In all, 75 patients were included in the study. Fifty-one patients were aged 65 to 74, and 24 patients were aged over 75. The majority of patients rated themselves as "completely independent" and "active," the highest levels of each. There was no difference in QuickDASH scores between those patients who rated themselves as completely partially independent, or active versus moderately active. There was no statistically significant difference in QuickDASH or range of motion parameters at final follow-up. Conclusions: This study demonstrates that, in a group of patients with high levels of independence and activity, outcomes are similar in patients aged 65 to 74 and over 75 at 1 year following distal radius ORIF.

BACKGROUND: The majority of retained syndesmotic screws will either loosen or break once the patient resumes weight-bearing. While evidence is limited, anecdotal experience suggests that intraosseous screw breakage may be problematic for some patients due to painful bony erosion. This study seeks to identify the incidence of intraosseous screw breakage, variables that may predict intraosseous screw breakage, and whether intraosseous screw breakage is associated with higher rates of implant removal secondary to pain.

METHODS: Five hundred thirty-one patients undergoing syndesmotic stabilization were screened, of which 43 patients (with 58 screws) experiencing postoperative screw breakage met inclusion criteria. Patient charts were retrospectively reviewed for demographic data, comorbidities, time to screw breakage, location of screw breakage, and implant removal. Several radiographic parameters were evaluated for their potential to influence the site of screw breakage.

RESULTS: Intraosseous screw breakage occurred in 32 patients (74.4%). Screw breakage occurred exclusively in the tibiofibular clear space in the remaining 11 instances (25.6%). Intraosseous screw breakage was significantly associated with eventual implant removal after breakage (P = .034). Screws placed further from the tibiotalar joint were at less risk for intraosseous breakage (odds ratio 0.818, P = .002). Screws placed at a threshold height of 20 mm or greater were more likely to break in the clear space (odds ratio 12.1, P = .002).

CONCLUSION: Syndesmotic screw breakage may be more problematic than previously described. Intraosseous breakage was associated with higher rates of implant removal secondary to pain in this study. Placement of screws 20 mm or higher from the tibiotalar joint may decrease risk of intraosseous breakage.Levels of Evidence: Level III: Retrospective study.

BACKGROUND: Treatment of distal radius fractures (DRFs) in patients aged >65 years is controversial. The purpose of this study was to identify what patient and fracture characteristics may influence the decision to pursue surgical versus nonsurgical treatment in patients aged >65 years sustaining a DRF.

METHODS: We queried our institutional DRF database for patients aged >65 years who presented to a single academic, tertiary center hand clinic over a 5-year period. In all, 164 patients treated operatively were identified, and 162 patients treated nonoperatively during the same time period were selected for comparison (total N = 326). Demographic variables and fracture-specific variables were recorded. Patient and fracture characteristics between the groups were compared to determine which variables were associated with each treatment modality (operative or nonoperative).

RESULTS: The average age in our cohort was 72 (SD: 11) years, and 274 patients (67%) were women. The average Charlson Comorbidity Index (CCI) was 4.1 (SD: 2.1). The CCI is a validated tool that predicts 1-year mortality based on patient age and a list of 22 weighted comorbidities. Factors associated with operative treatment in our population were largely related to the severity of the injury and included increasing dorsal tilt (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P < .001) and AO Classification type C fractures (OR, 5.42; 95% CI, 2.35-11.61; P < .001). Increasing CCI was the only factor independently associated with nonoperative management (OR, 0.84; 95% CI, 0.72-0.997; P = .046).

CONCLUSION: Fracture severity is a strong driver in the decision to pursue operative management in patients aged >65 years, whereas increasing CCI predicts nonoperative treatment.

Epithelioid sarcoma (ES) is a high-grade, soft tissue tumor of mesenchymal origin that rarely occurs in children and is often misdiagnosed as a benign entity. We present the case of a 12-year-old girl with a delayed diagnosis of ES of the left thumb. Radiological examination showed possible calcinosis from inflammation or traumatic injury. However, histopathological and immunohistochemistry studies showed findings consistent with a diagnosis of ES. She was treated with amputation of the interphalangeal joint of the left thumb. This case highlights the clinical and pathologic correlation required for the appropriate diagnosis and treatment of patients with soft tissue masses.

The management of distal radius fractures has evolved considerably in the last two decades. Techniques and hardware have improved so much that the surgeon can usually assure good results in these debilitating fractures. Yet no one method can be used for all injuries, as the personality of each fracture demands a customized approach. Furthermore, what works in one age group may not work in another. For this reason, every available treatment has its own space in our options. The need for surgeons to be well versed in all techniques is critical. We offer a concise update of important evolutionary and current treatment guidelines for this common fracture.

BACKGROUND: The purpose of this systematic review and meta-analysis is to compare the conservative and accelerated rehabilitation protocols in patients who underwent arthroscopic rotator cuff repair in terms of clinical outcomes and range of motions at 3, 6, 12, and 24-month follow-up.

METHODS: According to PRISMA guidelines, a systematic review of the literature was performed. For each included article, the following data has been extracted: authors, year, study design, level of evidence, demographic characteristics, follow-up, clinical outcomes, range of motions, and retear events. A meta-analysis was performed to compare accelerated versus conservative rehabilitation protocols after arthroscopic rotator cuff repair. The retear rate, postoperative Constant-Murley score and range of motions at 3, 6, 12, and 24 months of follow-up were the outcomes measured.

RESULTS: The search strategy yielded 16 level I-II clinical studies. A total of 1424 patients, with 732 patients and 692 in the accelerated and conservative group, were included. The average age (mean ± standard deviation) was 56.1 ± 8.7 and 56.6 ± 9 in the accelerated and conservative group. The mean follow-up was 12.5 months, ranging from 2 to 24 months. The meta-analysis showed no statistically significant differences in terms of retear rate between the groups (P = 0.29). The superiority of the accelerated group was demonstrated in terms of external rotation (P < 0.05) at 3-month follow-up; in terms of forward elevation, external rotation, abduction (P < 0.05), but not in terms of Constant-Murley score at 6-month follow-up; in terms of forward elevation (P < 0.05) at 12-month follow-up. No significant differences between the two group were highlighted at 24-month follow-up.

CONCLUSIONS: No statistically significant differences in the retear rate among the accelerated and conservative group have been demonstrated. On the other hand, statistically and clinically significant differences were found in terms of external rotation at 3 and 6 months of follow-up in favour of the accelerated group. However, no differences between the two groups were detected at 24 months follow-up.

UNLABELLED: Letters of recommendation (LORs) are highly influential in the residency selection process. Differences in language and length of LORs by gender have been demonstrated for applicants applying to surgical residencies and fellowships. This had yet to be studied in orthopaedic surgery. Given the gender disparity in the field, we sought to investigate the impact of gender on orthopaedic residency applicant LORs. We hypothesized that differences in length and language would be present for women applicants as compared to men.

METHODS: LORs for 2019 to 2020 applicants who applied to a single academic institution were selected for review. Female and male applicants were matched by medical school attended and United States Medical Licensing Examination Step 1 score. LORs were analyzed using both qualitative and quantitative analyses. Letters were evaluated for their word count, presence of language terms, and frequency of language terms. A similar subgroup language analysis was performed for standardized LORs (SLORs).

RESULTS: Six hundred fifty-six applicants met the initial screening criteria-126 women and 530 men. After matching, 71 female applicants were paired with 111 male applicants. Word count was, on average, longer for female applicants. LORs for female applicants were more likely to contain language terms that characterized their ability, achievement, participation in athletics, awards received, fit, leadership, and personality traits. Of these terms, ability and participation in athletics were also found more frequently in LORs written for women. In addition, language characterizing technical skills was found more frequently in LORs of female applicants. Similar codes were found to be statistically significant in the SLOR subgroup analysis.

CONCLUSION: This study highlights that current orthopaedic surgery residency LORs do not appear to be biased by applicant gender. LORs were longer for female applicants and described them more positively. Future female orthopaedic residency applicants should be assured that current female candidates are applying with at least similar if not greater subjective qualifications to their male counterparts based on the findings of this study.

Tendinopathy is a debilitating disease that causes as much as 30% of all musculoskeletal consultations. Existing treatments for tendinopathy have variable efficacy, possibly due to incomplete characterization of the underlying pathophysiology. Mechanical load can have both beneficial and detrimental effects on tendon, as the overall tendon response depends on the degree, frequency, timing, and magnitude of the load. The clinical continuum model of tendinopathy offers insight into the late stages of tendinopathy, but it does not capture the subclinical tendinopathic changes that begin before pain or loss of function. Small animal models that use high tendon loading to mimic human tendinopathy may be able to fill this knowledge gap. The goal of this review is to summarize the insights from in-vivo animal studies of mechanically-induced tendinopathy and higher loading regimens into the mechanical, microstructural, and biological features that help characterize the continuum between normal tendon and tendinopathy. STATEMENT OF SIGNIFICANCE: This review summarizes the insights gained from in-vivo animal studies of mechanically-induced tendinopathy by evaluating the effect high loading regimens have on the mechanical, structural, and biological features of tendinopathy. A better understanding of the interplay between these realms could lead to improved patient management, especially in the presence of painful tendon.