Citations

Abstract Background It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. Methods Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. Results Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). Conclusion Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.

Abstract KMT2A gene rearrangements are a major oncogenic driver in multiple hematologic neoplasms. Apart from t(9;11)(p21;q23) (KMT2A/MLLT3) in acute myeloid leukemia (AML), KMT2A gene rearrangements are considered to convey high risk and poor overall survival. Herein, we report a case of a 7 year old boy with newly diagnosed AML and a cryptic KMT2A/AFDN gene fusion resulting from a 5′KMT2A insertional event. The results of conventional chromosome studies revealed trisomy 8 in all 20 metaphases, with normal-appearing chromosomes 6 and 11. A KMT2A break-apart FISH probe identified 2 intact copies of the KMT2A gene region and an extra 5′KMT2A signal in 85% of interphase nuclei. Subsequent FISH studies using a KMT2A/AFDN dual-color dual-fusion FISH probe revealed positive results for a single fusion in 82% of interphase nuclei, indicating a KMT2A/AFDN gene fusion. Subsequently, metaphase FISH confirmed the location of the KMT2A/AFDN fusion at 6q27. To our knowledge, this represents only the second time in the literature that a cryptic KMT2A/AFDN gene fusion resulting from a 5′KMT2A insertional event was reported.

AbstractThe progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15‐99). Among them, 442 patients (12%) had core‐binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and ‐Y, and pneumonia as adverse prognostic factors for an early 4‐week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4‐week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low‐, high‐, and very high‐risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.

Background: The loss of extensor mechanism continuity that occurs with patellar and quadriceps tendon rupture has devastating consequences on patient function. Purpose: To describe a treatment strategy for extensor mechanism disruption and evaluate the outcomes of 3 techniques: primary repair, repair with semitendinosus tendon autograft augmentation, and reconstruction with Achilles tendon allograft. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed surgeries for extensor mechanism disruption performed by a single surgeon between 1999 and 2019. Patient characteristics, imaging studies, surgical techniques, and outcomes were recorded. Primary ruptures with robust tissue quality were repaired primarily, and first-time ruptures with significant tendinosis or moderate tissue loss were repaired using quadrupled semitendinosus tendon autograft augmentation. Patients with failed previous extensor mechanism repair or reconstruction and poor tissue quality underwent reconstruction with Achilles tendon allograft. The primary outcome was extensor mechanism integrity at a minimum 1-year follow-up, with extensor mechanism lag defined as >5° loss of terminal, active knee extension. Secondary outcomes included postoperative knee range of motion, International Knee Documentation Committee (IKDC) and Tegner activity scores, and the radiographic Caton-Deschamps Index. Results: Included were 22 patellar tendon and 21 quadriceps tendon surgeries (patients: 82.5% male; mean age, 48.1 years; body mass index, 31). Seventeen (39.5%) cases underwent primary tendon repair, 13 (30.2%) had repair using semitendinosus tendon autograft augmentation, and 13 (30.2%) underwent reconstruction using an Achilles tendon allograft. Seventeen (39.5%) cases had at least 1 prior failed extensor mechanism surgery performed at an outside facility. At the last follow-up, 4 (9.3%) cases had an extensor mechanism lag, no cases required additional extensor mechanism surgery, and all cases were able to achieve >90° of knee flexion. Postoperative IKDC scores were significantly improved with all methods of extensor mechanism surgery, and postoperative Tegner activity scores were significantly improved in patients who underwent primary repair and Achilles tendon allograft reconstruction ( P < .05 for all). Conclusion: Primary repair alone, repair using quadrupled semitendinosus tendon autograft augmentation, and reconstruction using Achilles tendon allograft were all effective methods to restore extensor mechanism and knee function with the proper indications. Persistent knee extensor lag was more common in chronic extensor mechanism injuries after failed surgery, although patients still reported significantly improved postoperative functional outcomes.

Purpose To determine whether elbow torque was associated with anatomic adaptations of the medial elbow following a season of competitive pitching. Methods Pitchers from 3 collegiate baseball teams were recruited during the preseason for participation. Before the season, pitchers were recorded throwing 5 “game‐speed” fastball pitches from a standard distance off a mound while wearing a wearable sensor baseball compression sleeve that calculates elbow torque, arm speed, arm slot, and arm rotation. Participants subsequently underwent dynamic ultrasound imaging of the medial elbow, including measurements of the ulnar collateral ligament (UCL) and ulnohumeral joint space to assess elbow laxity. Following a full season of competitive pitching, all testing was repeated, and statistical analysis comparing preseason to postseason sonographic findings was performed. Results Twenty‐eight collegiate pitchers underwent preseason sonographic and kinematic testing. Nineteen pitchers were available for postseason testing. The average age (standard deviation) and playing experience was 19.9 (1.2) and 14.7 (1.5) years. Compared with preseason, there were significant increases in postseason UCL thickness (1.92 ± 0.09 vs 1.56 ± 0.09 mm, P < .01) and elbow laxity (1.77 ± 0.23 vs 1.15 ± 0.22 mm, P = .028) after a season of pitching. No significant changes in pitching kinematic measurements were observed between preseason and postseason testing. Preseason pitching kinematic measurements were significantly associated with increased UCL thickness (arm slot: beta estimate –0.03 ± 0.01, P = .011) and reduction in elbow laxity (elbow torque: beta estimate –0.03 ± 0.01, P = .04) after a season of pitching. Pitchers with increased body weight and arm length demonstrated reduced medial elbow torque during pitching ( P < .05). Conclusions After a season of competitive pitching, adaptive changes of the medial elbow were demonstrated on dynamic ultrasound. However, the influence of pitching kinematic measurements on these adaptations are of small magnitude and unknown clinical significance. Although wearable sensor technology may have value in trending individual pitcher kinematics, no discrete threshold appears to predict the development of adaptive changes at the elbow. Level of Evidence Level II, prospective observational study.

Abstract Background: Sickle cell disease (SCD) is a life-limiting inherited hemoglobinopathy that results in significant complications and affects quality of life. Hematopoietic stem cell transplantation (HSCT) is currently the only curative intervention for SCD; however, guidelines are needed to inform how to apply HSCT in clinical practice. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and health professionals in their decisions about HSCT for SCD. Methods: The multidisciplinary guideline panel formed by ASH included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews (through 2019). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT. Conclusions: The evidence review yielded no randomized controlled clinical trials for HSCT in SCD; therefore, all recommendations are based on very low certainty in the evidence. Key recommendations include considering HSCT for those with neurologic injury or recurrent acute chest syndrome at an early age and to improve nonmyeloablative regimens. Future research should include the development of a robust SCD registry to serve as a comparator for HSCT studies.

Background: Data regarding opioid prescribing patterns following pediatric orthopaedic procedures is limited. The aim of this work was to evaluate the effects of tiered guidelines for discharge opioid prescriptions following common pediatric orthopaedic procedures. Methods: Quality improvement project conducted at a single academic institution. Guidelines for discharge opioid prescriptions were implemented January 2018 and established 4 tiers of increasing invasiveness for 28 common pediatric orthopaedic procedures. Patients who underwent these procedures in 2017 comprised the preguideline cohort (N=258), while patients treated in 2019 comprised the postguideline cohort (N=212). Opioid prescriptions were reported as oral morphine equivalents (OMEs). Univariate tests were performed to assess statistically significant differences before and after implementation of the guidelines. Results: There was a significant decrease in OME prescribed between preguideline and postguideline cohorts (median OME 97.5 vs. 37.5). When analyzed according to procedure tiers, tiers 1, 2, and 4 showed significant decreases in OME prescribed between 2017 and 2019. The rate of no opioids prescribed at discharge increased from 13% to 23% between preguideline and postguideline cohorts. The 30-day refill rate did not significantly change. After implementation of guidelines, 91% of all prescriptions were within the guideline parameters, and there was a significant reduction in prescription variability. In tier 4 procedures, median OME prescribed decreased from 375 preguideline to 188 postguideline, but was associated with greater opioid refills within 30 days of discharge (10.2% preguideline vs. 28.8% postguideline). Conclusions: Tiered guidelines for discharge opioid prescriptions following pediatric orthopaedic procedures can significantly decrease the quantity of opioids prescribed. Furthermore, we noted excellent adherence and no overall increase in the rates of narcotic refills. Such guidelines may improve pediatric orthopaedists’ ability to responsibly treat postoperative pain while limiting the distribution of unneeded opioids. Level of Evidence: Level IV—quality improvement project.

Abstract Aims We sought to determine whether the Diamond–Forrester classification using non-invasive haemodynamic measurements by 2-D and Doppler echocardiography would predict hospital mortality in cardiac intensive care unit (CICU) patients. Methods and results We retrospectively analysed unique patients admitted to the CICU at Mayo Clinic Rochester from 2007 to 2018. Doppler-derived cardiac index (CI) and ratio of mitral valve E velocity to medial mitral annulus e′ velocity (E/e′ ratio) were used to classify patients into four profiles: Profile I (warm/dry), Profile II (warm/wet), Profile III (cold/dry), and Profile IV (cold/wet). Logistic regression was used to determine predictors of hospital mortality, and Cox proportional-hazards analysis was used to determine predictors of mortality during one year of follow-up. We included 4563 patients with a mean age of 68.3 ± 14.3 years, including 36.2% female patients. The distribution of each profile was as follows: I, 47.4%; II, 36.2%; III, 7.9%; IV, 8.5%. A total of 5.8% patients died during hospitalization, and 18.1% died by 1 year. Patients with either low CI or elevated E/e′ ratio had higher in-hospital and 1 year mortality. Patients with elevated E/e′ ratio (i.e. Profiles II and IV) had an increased risk of death during hospitalization and at 1 year after multivariate adjustment (adjusted hazard ratio 1.72 and 2.17 for 1 year mortality, respectively, compared with Profile I, P &lt; 0.01). Conclusions Simple Doppler echocardiographic assessment can be used to identify haemodynamic profiles defined by the Diamond–Forester classification in patients admitted in CICU. These profiles predict outcomes and may be used to guide therapy in critically ill patients.