Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma.

Anaplastic lymphoma kinase ( ALK )-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1 - unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation. Crizotinib can successfully be used to treat unresectable novel ALK fusion sarcomas.

Rate of Rise of Platelet Count After IVIG for Pediatric Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease causing platelet destruction, and is a common cause of symptomatic thrombocytopenia in children. Intravenous immune globulin (IVIG) is a treatment for ITP that increases the platelet counts of most patients within 24 to 48 hours. This study aimed to calculate the rate of rise in pediatric ITP after a dose of IVIG and to analyze if patient characteristics affected the rate. For 116 children treated for ITP with IVIG at Hershey Medical Center, the rate of rise of the platelet count for all patients was calculated. The rate of rise ranged from -0.1 to +4.2 K/µL/hour (average 1.3, median 1.2). 78% of patients had a rate of rise of over 0.5 K/µL/hour. There was a statistically significant correlation between the rate rise of the platelet count and the initial platelet count (P=0.0197), but rate was not affected by age or sex. This study was able to demonstrate that IVIG is effective in most patients and that demographic features do not affect the rate of rise. By providing a nomogram showing when to expect a meaningful rise in the platelet count after IVIG, we give guidance for timing of the postinfusion platelet count to avoid administering a second dose. Future studies are needed to test this nomogram prospectively.

The Impact of an Unconventional Elective in Narrative Medicine and Pediatric Psycho-oncology on Humanism in Medical Students.

Over the course of medical school, students' optimism and hopefulness often devolve into a cynical view of medicine that continues throughout clinical rotations and beyond (Neumann et al., Acad Med 86(8):996-1009, 2011). Here, we present a qualitative evaluation of a novel immersive elective in pediatric psycho-oncology coupled with narrative medicine and its impact on students. Participants were third- and fourth-year medical students who were relieved of traditional clinical duties. Alternatively, they shadowed pediatric cancer patients, keeping narrative journals of their observations and insights. A trained team of pre-clinical medical students and faculty conducted a retrospective analysis of 120 journals written between 2008 and 2019. They compared recurring concepts to assess how blending experiential learning and reflective writing influenced the attitudes and behaviors of students. Consistent themes emerged related to developing a rich understanding of patient experiences, a humanistic appreciation of the context of illness, the ability to meaningfully reflect on insights to critically ill children, and an appreciation for the unique learning opportunity. Additionally, families expressed gratitude for the students' attentiveness to their emotional needs. By the conclusion of the elective, most students discovered that they had reignited their intrinsic empathic behaviors and were provided with beneficial insights that they believed would continue into future rotations. Experiential teaching methods paired with narrative reflection may be a valuable and therapeutic tool to learn the intricacies of the patient perspective, with the potential to enhance humanism in students during a critical time in their medical training when empathy tends to drift. Longitudinal and quantitative studies are warranted to better understand the degree and duration of specific benefits.

Shared Decision-Making Is Associated with Better Outcomes in Patients with Knee But Not Hip Osteoarthritis: The DECIDE-OA Randomized Study.

BACKGROUND: Current guidelines recommend shared surgical decision-making, yet it is unclear whether shared decision-making improves health outcomes in patients who are considering knee and hip replacement. The purpose of the present study was to examine whether patients who made high-quality, informed, patient-centered (IPC) decisions had better health outcomes, higher satisfaction, and less decision regret compared with those who made lower-quality decisions. METHODS: A multisite, randomized study of 2 decision aids for patients with hip and knee osteoarthritis was utilized to collect data on decision-making and health outcomes at 2 time points: shortly after the initial surgical evaluation and about 6 months after treatment. We calculated the percentage of patients who made an IPC decision and examined the a priori hypotheses that IPC decisions would be associated with better health outcomes, satisfaction, and less regret at 6 months. Linear and logistic regression models were utilized to examine the relationships. RESULTS: The analytic sample included 854 patients with a mean age of 65 years (standard deviation, 9 years), of whom 58% were female, 93% were White non-Hispanic, 67% had knee (compared with hip) osteoarthritis, and 62% underwent operative treatment within 6 months of the initial evaluation. The majority of patients (68%) made IPC decisions. The IPC group had significantly larger gains in quality of life (mean difference in EuroQol-5 Dimension, 0.04; 95% confidence interval [CI], 0.02 to 0.07; p < 0.001) compared with the non-IPC group. For knee patients, the IPC group also had significantly better Knee injury and Osteoarthritis Outcome Scores (mean difference, 4.9; 95% CI, 1.5 to 8.3; p = 0.004), higher satisfaction (adjusted odds ratio [aOR], 1.7; 95% CI, 1.2 to 2.3; p = 0.003), much better pain relief (aOR, 2.1; 95% CI, 1.3 to 3.5; p = 0.002), and were more likely to have no decision regret (aOR, 2.3; 95% CI, 1.3 to 4.1; p = 0.003). For hip patients, IPC decisions were not associated with better Harris hip scores or satisfaction and were associated with more regret. CONCLUSIONS: Higher-quality decisions predicted small improvements in health outcomes, as well as greater satisfaction and less regret for patients with knee osteoarthritis, but not for patients with hip osteoarthritis. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Novel fusion sarcomas including targetable NTRK and ALK.

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

Variation in perioperative opioid use after total joint arthroplasty.

OBJECTIVE: We studied variation in perioperative opioid use after total joint arthroplasty with respect to patient and procedure characteristics in order to inform initiatives to optimize pain relief. METHODS: We recorded perioperative opioid consumption for a cohort of total joint arthroplasty patients to identify factors underlying variation in perioperative opioid use. RESULTS: Younger patient age, tobacco use, greater symptoms of depression, private insurance, and knee arthroplasty were associated with increased opioid consumption. CONCLUSIONS: Awareness of the patient characteristics associated with increased perioperative opioid use can help inform implementation of targeted strategies for safe, optimal pain relief and satisfaction.

Validation of an electronic coding algorithm to identify the primary indication of orthopedic surgeries from administrative data.

BACKGROUND: Determining the primary indication of a surgical procedure can be useful in identifying patients undergoing elective surgery where shared decision-making is recommended. The purpose of this study was to develop and validate an algorithm to identify patients receiving the following combinations of surgical procedure and primary indication as part of a study to promote shared decision-making: (1) knee arthroplasty to treat knee osteoarthritis (KOA); (2) hip arthroplasty to treat hip osteoarthritis (HOA); (3) spinal surgery to treat lumbar spinal stenosis (SpS); and (4) spinal surgery to treat lumbar herniated disc (HD). METHODS: Consecutive surgical procedures performed by participating spine, hip, and knee surgeons at four sites within an integrated care network were included. Study staff reviewed electronic medical records to ascertain a "gold standard" determination of the procedure and primary indication status. Electronic algorithms consisting of ICD-10 and CPT codes for each combination of procedure and indication were then applied to records for each case. The primary measures of validity for the algorithms were the sensitivity and specificity relative to the gold standard review. RESULTS: Participating surgeons performed 790 procedures included in this study. The sensitivity of the algorithms in determining whether a surgical case represented one of the combinations of procedure and primary indication ranged from 0.70 (HD) to 0.92 (KOA). The specificity ranged from 0.94 (SpS) to 0.99 (HOA, KOA). CONCLUSION: The electronic algorithm was able to identify all four procedure/primary indication combinations of interest with high specificity. Additionally, the sensitivity for the KOA cases was reasonably high. For HOA and the spine conditions, additional work is needed to improve the sensitivity of the algorithm to identify the primary indication for each case.

Celestial Versus Terrestrial Travel-An Analysis of Spaceflight Fatalities and Comparison to Other Modes of Transportation.

With the advent of commercial human spaceflight, it is important to analyze the historical safety of humans traveling to, in, and from space. We break down the fatality rates of human spaceflight and compare them to those of several terrestrial transportation modes. We created a database of human space travel, containing the vehicles, launches, and the total time and distance traveled. For the 4 fatal space missions and 18 fatalities, we determined the fatality rates, calculated by several methods, including rates per trip, person, and distance traveled, stratified by the mission segment affected. Two of the 326 launches did not reach space, and 8 others were suborbital. There have been 1285 person-launches to space; the total time in space is estimated to be 55,939 person-days; and the total distance traveled is approximately 23.5 billion person-miles. One fatal trip occurred on the way to orbit and the other 3 during the return. There has yet to be a fatality in orbit, and there have been none on any space flight since 2003. The per-trip and per-person fatality rates are 1.2% and 1.4%, respectively, but the per mile rate is much lower, depending on the flight segment.

Why We Sleep: A Hypothesis for an Ultimate or Evolutionary Origin for Sleep and Other Physiological Rhythms.

Although sleep is ubiquitous, its evolutionary purpose remains elusive. Though every species of animal, as well as many plants sleep, theories of its origin are purely physiological, e.g. to conserve energy, make repairs or to consolidate learning. An evolutionary reason for sleep would answer one of biology's fundamental unanswered questions. When environmental conditions change on a periodic basis (winter/summer, day/night) organisms must somehow confront the change or else be less able to compete in either niche. Seasonal adaptation includes the migration of birds, changes in honeybee physiology and winter abscission in plants. Diurnal adaptation must be more rapid, forcing changes in behavior in addition to physiology. Since organisms must exist in both environments, evolution has created a way to force a change in behavior, in effect creating "different" organisms (one awake, one asleep) adapted separately to two distinct niches. We sleep to allow evolving into two competing niches. The physiology of sleep forces a change to a different state for the second niche. The physiological needs for sleep are mechanisms that have evolved to achieve this goal.

Decision Support Strategies for Hip and Knee Osteoarthritis: Less Is More: A Randomized Comparative Effectiveness Trial (DECIDE-OA Study).

BACKGROUND: As guidelines and payers increasingly recommend use of patient decision aids (DAs), evidence about the comparative effectiveness of available DAs is critical for organizations interested in implementing them. The primary purpose of this study was to compare 2 DAs with regard to their ability to help patients become informed and receive their preferred treatment (that is, make an informed patient-centered decision), shared decision-making, surgical rates, and surgeon satisfaction. METHODS: We performed a multisite factorial randomized trial enrolling patients with hip or knee osteoarthritis. Patients were randomly assigned to use a long, detailed DA (long DA) or short, interactive DA (short DA). Eight surgeons were randomly assigned to receive a patient preference report detailing the patient's goals and treatment preferences or to administer usual care. RESULTS: We distributed 1,636 pre-visit surveys, 1,220 of which were returned (75% response rate), and 1,124 post-visit surveys, 967 of which were returned (86% response rate). The patients in the sample had a mean age (and standard deviation) of 65 ± 10 years, 57% were female, 89% were white non-Hispanic, and 67% had knee osteoarthritis. The majority (67.2%) made informed patient-centered decisions, and the rate did not vary significantly between the DA groups (p = 0.97) or between the surgeon groups (p = 0.23). Knowledge scores were higher for the short-DA group (mean difference = 9%; p < 0.001). More than half of the sample (60.5%) had surgery within 6 months after the visit, and rates did not differ significantly by DA or surgeon group. Overall, the surgeons were highly satisfied and reported that the majority (88.7%) of the visits were of normal duration or shorter. CONCLUSIONS: The DECIDE-OA study is, to our knowledge, the first randomized comparative effectiveness study of 2 orthopaedic DAs. The short DA outperformed the long DA with regard to knowledge scores and was comparable with respect to other outcomes. The surgeons reported high satisfaction and normal visit duration with both DAs. CLINICAL RELEVANCE: Surgeons need to ensure that patients with osteoarthritis are well-informed and have a clear preference regarding whether to undergo hip or knee replacement surgery. The DAs used in this study may help surgeons involve patients in elective surgery decisions and meet the requirements of informed consent.

Early post-operative opioid consumption: A comparison between medial unicompartmental, patellofemoral, and total knee arthroplasty.

BACKGROUND: While there is emerging literature describing the use of narcotics for post-operative pain control following TKA, little data is available regarding narcotic use in partial knee replacements. The aim of this study is to compare the early post-operative narcotic requirements after medial compartmental arthroplasty (UKA) and patellofemoral arthroplasty (PFA) with that of TKA. METHODS: In this retrospective chart review, we identified 37 patients who underwent PFA and 71 patients who underwent UKA. We identified a cohort of TKA patients who were matched to the unicompartmental group based on sex and age (n = 108). The primary outcome measure was self-reported use of opioids for pain management at the first post-operative clinic visit. Opioid use between groups was compared using Chi-square analysis. RESULTS: The PFA group was younger (p < 0.001) and consisted of more females (p < 0.001) than the UKA group. The UKA cohort had more non-smoking patients (p = 0.044) compared to the PFA cohort. Self-reported opioid use at the first post-operative visit differed between the three groups of patients (p < 0.001). A greater proportion of both PFA (38% vs. 11%; p < 0.001) and TKA (41% vs. 11%; p = 0.01) patients reported opioid use when compared to UKA patients. No differences in opioid use existed between TKA and PFA groups (p = 0.61). CONCLUSION: The prevalence of PFA patients who report opioid use at the first post-operative visit is similar to that for patients following TKA, suggesting that pain management protocols for this specific subset of partial knee arthroplasty patients should be structured similar to TKA patients and separate from UKA patients.

Pilot Study Examining Feasibility and Comparing the Effectiveness of Decision Aids for Hip and Knee Osteoarthritis: A Randomized Trial.

Background. There are many patient decision aids (DAs) available, yet there is limited evidence on comparative effectiveness of different tools. Objective. To examine feasibility of a study protocol and gather preliminary data on comparative effectiveness. Methods. Adult patients seeing a surgeon to discuss treatment for hip or knee osteoarthritis were randomized to hip and knee DAs from two vendors. Pre-visit survey included Hip/Knee Decision Quality Instrument, DA usage, health literacy, and quality of life (EQ-5D). Surgical status was ascertained 6 months post-visit. We examined response rates, eligibility, and compared the two DAs on amount of use, knowledge scores, and receipt of preferred treatment. Results. Overall response rate was 58/74 (78%) and did not differ by study arm. More patients in DA-A group reported reviewing all the DAs (64.5% DA-A v. 24.0% DA-B, P = 0.003). Knowledge scores were similar across arms (55.2% DA-A v. 48.8% DA-B, P = 0.4). For DA-B, knowledge scores were higher for those who reviewed all the DAs compared with those who did not (80% knowledge v. 39% knowledge, respectively, P = 0.004), while scores for DA-A did not vary by usage (62% knowledge v. 53% knowledge, respectively, P = 0.3). A similar percentage of each group received their preferred treatment (77% v. 73%, P = 0.8). Patients who were unsure about preferred treatment at baseline were more likely to have surgery in the DA-A arm compared with the DA-B arm (55% v. 20%, P = 0.1). Limitations. Small sample; patients were only surveyed pre-visit. Conclusion. Despite having different content and formats, the two DAs had similar overall effectiveness. Patients were more likely to review all of DA-A; however, patients who reviewed all of DA-B had the highest knowledge scores.

Protocol for a randomised trial evaluating the comparative effectiveness of strategies to promote shared decision making for hip and knee osteoarthritis (DECIDE-OA study).

INTRODUCTION: There are several different interventions available to promote shared decision making (SDM); however, little is known about the comparative effectiveness of different approaches. OBJECTIVE: To examine the impact of patient-directed and physician-directed decision support strategies on the quality of treatment decisions for hip and knee osteoarthritis (OA). TRIAL DESIGN: A 2×2 factorial randomised controlled trial. SETTING: One academic medical centre, one community hospital and one orthopaedic specialty hospital. PARTICIPANTS AND INTERVENTIONS: The enrolment targets were 8 surgeons and 1120 patients diagnosed with hip or knee OA. Patients were randomly assigned to receive one of two different decision aids (DAs) stratified by site. The DAs varied in length, content and the level of detail regarding treatment options. Both DAs were available by paper or online.Surgeons were randomly assigned to receive a report detailing patients' goals and treatment preferences at the time of the visit or not. Eligible patients received their assigned DA before their visit and completed three surveys: before the visit (timepoint (T)1), 1-week postvisit (T2) and 6 months from either the visit date or surgery date for patients who underwent surgery (T3). Study staff and participating surgeons were not blinded, but the statistician conducting the analyses was blinded to the arms. MAIN OUTCOME MEASURE AND ANALYSIS: The primary study outcome was decision quality, the percentage of patients who were well informed and received their preferred treatment. Secondary outcomes included involvement in decision making, surgical rates, health outcomes, decision regret and satisfaction. A logistic regression model with the generalised estimating equations approach was used to compare rates of decision quality between the groups and account for the clustering of patients within providers. ETHICS AND DISSEMINATION: Ethics approval was obtained through the institutional review board at the main site. The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02729831; Pre-results.

The Impact of Medical Comorbidities on Primary Total Knee Arthroplasty Reimbursements.

Medical comorbidities have been shown to cause an increase in peri-and postoperative complications following total knee arthroplasty (TKA). However, the increase in cost associated with these complications has yet to be determined. Factors that influence cost have been of great interest particularly after the initiation of bundled payment initiatives. In this study, we present and quantify the influence of common medical comorbidities on the cost of care in patients undergoing primary TKA. A retrospective level of evidence III study was performed using the PearlDiver supercomputer to identify patients who underwent primary TKA between 2007 and 2015. Patients were stratified by medical comorbidities and compared using analysis of variance for reimbursements for the day of surgery and over 90 days postoperatively. A cohort of 137,073 US patients was identified as having undergone primary TKA between 2007 and 2015. The mean entire episode-of-care reimbursement was $23,701 (range: $21,294-26,299; standard deviation [SD] $2,611). The highest reimbursements were seen in patients with chronic obstructive pulmonary disease (mean $26,299; SD $3,030), hepatitis C (mean $25,662; SD $2,766), morbid obesity (mean $25,450; SD $2,154), chronic kidney disease (mean $25,131, $3,361), and cirrhosis (mean $24,890; SD $2,547). Medical comorbidities significantly impact reimbursements, and therefore cost, after primary TKA. Comprehensive preoperative optimization for patients with medical comorbidities undergoing TKA is highly recommended and may reduce perioperative complications, improve patient outcome, and ultimately reduce cost.

Informed, Patient-Centered Decisions Associated with Better Health Outcomes in Orthopedics: Prospective Cohort Study.

BACKGROUND: A goal of shared decision making (SDM) is to ensure patients are well informed and receive preferred treatments. However, the relationship between SDM and health outcomes is not clear. OBJECTIVE: The purpose was to examine whether patients who are well informed and receive their preferred treatment have better health outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study at an academic medical center surveyed new patients with knee or hip osteoarthritis, herniated disc, or spinal stenosis 1 week after seeing a specialist and again 6 months later. Main Outcomes and Measures. The survey assessed knowledge, preferred treatment, and quality of life (QoL). The percentage of patients who were well informed and received preferred treatment was calculated (informed, patient centered [IPC]). A follow-up survey assessed QoL, decision regret, and satisfaction. Regression analyses with generalized estimating equations to account for clustering tested a priori hypotheses that patients who made IPC decisions would have higher QoL. RESULTS: Response rate was 70.3% (652/926) for initial and 85% (551/648) for follow-up. The sample was 63.9 years old, 52.8% were female, 62.6% were college educated, and 49% had surgery. One-third (37.4%) made IPC decisions. Participants who made IPC decisions had significantly better overall (0.05 points (SE 0.02) for EQ-5D, P = 0.004) and disease-specific quality of life (4.22 points [SE 1.82] for knee, P = 0.02; 4.46 points [SE 1.54] for hip, P = 0.004; and 6.01 points [SE 1.51] for back, P < 0.0001), higher satisfaction and less regret. LIMITATIONS: Observational study at a single academic center with limited diversity. CONCLUSIONS: Well-informed patients who receive their preferred treatment also had better health outcomes and higher satisfaction.

Cadaver-Specific Models for Finite-Element Analysis of Iliopsoas Impingement in Dual-Mobility Hip Implants.

BACKGROUND: Joint dislocation is a major cause of failure in total hip arthroplasty. Dual-mobility implants provide a femoral head diameter that can match the native hip size for greater stability against dislocation. However, such large heads are prone to impingement against surrounding soft tissues. To address this concern, the concept of an anatomically contoured dual-mobility implant was evaluated using cadaver-specific finite-element analysis (FEA). METHODS: The stiffness of 10 iliopsoas tendons was measured and also 3D bone models, contact pressure, and iliopsoas tendon stress were evaluated for 2 implant designs according to a previous cadaveric experiment. The iliopsoas interaction with an anatomically contoured and conventional dual-mobility implant was analyzed throughout hip flexion. RESULTS: The tensile test of cadaveric iliopsoas tendons revealed an average linear stiffness of 339.4 N/mm, which was used as an input for the FEA. Tendon-liner contact pressure and tendon von Mises stress decreased with increasing hip flexion for both implants. Average contact pressure and von Mises stresses were lower in the anatomically contoured design compared with the conventional implant across all specimens and hip flexion angles. CONCLUSIONS: This study was built upon a previous cadaver study showing reduced tenting of the iliopsoas tendon for an anatomically contoured design compared with a conventional dual-mobility implant. The present cadaver-specific FEA study found reduced tendon-liner contact pressure and tendon stresses with contoured dual-mobility liners. Anatomical contoured design may be a solution to avoid anterior soft-tissue impingement when using hip prostheses with large femoral heads.