Citations

Background: Shoulder and elbow function is essential to basic basketball actions. Outside of anterior shoulder instability, injuries in these joints are not well characterized in National Basketball Association (NBA) players. Purpose: To describe the epidemiology and associated risk factors of shoulder and elbow injuries in NBA players and identify factors that influence player performance upon return to play. Study Design: Descriptive epidemiology study. Methods: Historical injury data from the 2015-2020 NBA seasons were retrieved from Pro Sports Transactions, a public online database. An injury was defined as a health-related concern resulting in an absence of ≥1 NBA games. Primary measures included pre- and postinjury player efficiency rating (PER) and true shooting percentage (TS%) with interquartile ranges (IQRs), stratified by extremity dominance. Multivariate logistic regression analyses with stepwise regression were performed to identify risk factors associated with return-to-play performance. Results: A total of 192 shoulder and elbow injuries were sustained among 126 NBA athletes, with incidence rates of 1.11 per 1000 game exposures (GEs) and 0.30 per 1000 GEs, respectively. Sprain/strain and general soreness were the most common injury types in both the shoulder and the elbow. In the 2 years after injury, baseline PER was achieved in all groups, except for players with dominant shoulder injuries (baseline PER, 16 [IQR, 14-18] vs 2-year PER, 13 [IQR 11-16]; P = .012). Younger age was associated with quicker return to baseline PER (odds ratio, 0.77 [95% CI, 0.67-0.88]). Shoulder and elbow injuries did not negatively influence TS% upon return to play (baseline TS%, 0.55% [IQR, 0.51%-0.58%] vs 1-year TS%, 0.55% [IQR, 0.52%-0.58%]; P = .13). Conclusion: Dominant shoulder injuries negatively influenced PER during the first 2 seasons upon return to play in NBA players. Therefore, expectations that players with this type of injury immediately achieve baseline statistical production should be tempered. Shooting accuracy appears to remain unaffected after shoulder or elbow injury.

Abstract Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiD). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window. By combining IMiDs with EP300 inhibition, we demonstrate greater downregulation of MYC and IRF4, synergistic killing of myeloma in vitro and in vivo, and an increased therapeutic window. Interestingly, this potent combination failed where MYC and IRF4 expression was maintained by high levels of the AP-1 factor BATF. Our results identify an effective drug combination and a previously unrecognized mechanism of IMiD resistance. Significance: These results highlight the dependence of MM on IKZF1-bound super-enhancers, which can be effectively targeted by a potent therapeutic combination pairing IMiD-mediated degradation of IKZF1 and IKZF3 with EP300 inhibition. They also identify AP-1 factors as an unrecognized mechanism of IMiD resistance in MM. See related article by Neri, Barwick, et al., p. 56. See related commentary by Yun and Cleveland, p. 5. This article is featured in Selected Articles from This Issue, p. 4

Introduction: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative carbohydrate antigen 19.9 (CA 19.9) in predicting the N+ stage in resectable-PDAC (R-PDAC). Methods: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analysed. A preoperative laboratory value of CA 19.9 greater than 37 U/l was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA 19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. Results: A total of 2034 PDs from thirteen centres were included in the study. CA 19.9 greater than 37 U/l was significantly associated with higher N+ at univariate and multivariate analysis ( P <0.001). CA 19.9 levels greater than 37 U/l were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumours and with higher cut-off values for all cT stages. Conclusion: Lymph-nodal involvement is strongly related to preoperative CA 19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA 19.9 values should be considered in a more biologically advanced stage.

Abstract BACKGROUND Differentiating radiation necrosis from tumour progression after radiation therapy (RT) for brain metastases (BM) remains clinically challenging, and accurate imaging is crucial to prevent unnecessary surgery or unwarranted changes in therapy. 18F-Fluciclovine is a PET radiopharmaceutical with low background uptake in the brain and increased uptake in BM. The PURSUE study (NCT04410367) aimed to establish image interpretation criteria (IIC) for detecting suspected recurrent BM after RT using 18F-fluciclovine PET, based on several measures of lesion uptake. MATERIAL AND METHODS Across 7 US sites, 23 patients with solid tumour BM and a previously irradiated ‘reference’ lesion equivocal for recurrence on MRI who were scheduled for craniotomy underwent 18F-fluciclovine PET (185 MBq) &lt;42 days post-MRI and 1-21 days pre-craniotomy. Three independent, blinded readers qualitatively rated lesion 18F-fluciclovine uptake as ‘mild’ (up to blood pool), ‘moderate’ (above blood pool to parotid gland), or ‘marked’ (above parotid gland). The primary endpoint was the diagnostic performance of different thresholds of lesion uptake on qualitative (visual) reads vs central histopathology. Secondary endpoints included diagnostic performance, based on different thresholds, of quantitative (e.g., lesion standardized uptake value [SUV]), and dynamic measures. A committee, including two independent imaging physicians, reviewed all data to establish the IIC, which were subsequently used to evaluate the diagnostic performance of 18F-fluciclovine. RESULTS All 23 reference lesions underwent histopathological analysis, with 10 (43%) being pathologically confirmed BM recurrence. The highest performing qualitative measure of 18F-fluciclovine lesion uptake was ‘marked’, rendering 92-100% and variable (40-80%) across readers. SUVmax was a reader-independent, high-performing quantitative metric (AUC 0.87, SUVmax threshold 4.8, 80% sensitivity, 85% specificity). Dynamic measures did not add diagnostic value. Thus, the committee established IIC as: "Lesions with 18F-fluciclovine uptake of a SUVmax equal to or greater than 4.8, or visually greater than the parotid gland, should be considered suspicious for recurrence. Otherwise, recurrence should be considered unlikely." Application of these IIC resulted in 80% sensitivity, 77-85% specificity, 73-80% positive predictive value, and 83-85% negative predictive value across readers. CONCLUSION PURSUE is the first prospective, multicentre study to define IIC for 18F-fluciclovine PET for accurate identification of suspected recurrent BM after RT, verified by histopathology. In this initial cohort, the IIC convey excellent diagnostic performance for 18F-fluciclovine and will help evaluate 18F-fluciclovine PET in future studies. This study was sponsored by Blue Earth Diagnostics Ltd.

Abstract In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

Abstract BACKGROUND After radiation therapy (RT) for brain metastases (BM), differentiating radiation necrosis from tumor recurrence remains challenging. PURSUE (NCT04410367) evaluated various measures of lesion 18F-fluciclovine uptake to establish image interpretation criteria (IIC) for 18F-fluciclovine-PET to accurately diagnose recurrent BM. METHODS Patients with solid tumor BM and a previously irradiated ‘reference’ lesion equivocal for recurrence on MRI who were scheduled for craniotomy underwent 18F-fluciclovine-PET (185 MBq) &lt;42 days post-MRI and 1-21 days pre-craniotomy. Lesion 18F-fluciclovine uptake was qualitatively rated as ‘mild’ (up to blood pool), ‘moderate’ (above blood pool to parotid gland), or ‘marked’ (above parotid gland) by three independent blinded readers. The primary endpoint was diagnostic performance of different uptake thresholds on qualitative reads vs central histopathology. Secondary endpoints included diagnostic performance, based on different thresholds, of quantitative (e.g., lesion standardized uptake value [SUV]) and dynamic measures. IIC were determined by committee and subsequently used to assess the diagnostic performance of 18F-fluciclovine. RESULTS All 23 reference lesions from 23 enrolled patients underwent histopathological analysis; 10 (43%) were pathologically-confirmed BM recurrence. The highest performing qualitative measure was ‘marked’, rendering 92-100% sensitivity and 40-80% specificity across readers. SUVmax was a reader-independent, high-performing quantitative metric (AUC 0.87, SUVmax threshold 4.8, 80% sensitivity, 85% specificity). Dynamic measures did not add diagnostic value. Thus, IIC was established as: “Lesions with 18F-fluciclovine uptake of SUVmax equal to or greater than 4.8, or visually greater than the parotid gland, should be considered suspicious for recurrence. Otherwise, recurrence should be considered unlikely.” Application of the IIC resulted in 80% sensitivity, 77-85% specificity, 73-80% PPV, and 83-85% NPV across the readers. CONCLUSIONS PURSUE is the first prospective, multicenter trial to establish IIC for 18F-fluciclovine-PET for suspected recurrent BM after RT, verified by histopathology. Finalized IIC demonstrated excellent diagnostic performance for 18F-fluciclovine and will help evaluate 18F-fluciclovine-PET in future studies.

Background: Ankle injuries are more common in the National Basketball Association (NBA) compared with other professional sports. Purpose/Hypothesis: The purpose of this study was to report the incidence and associated risk factors of ankle injuries in NBA athletes. It was hypothesized that factors associated with an increased physiologic burden, such as minutes per game (MPG), usage rate, and associated lower extremity injury, would be associated with increased ankle injury risk and time loss. Study Design: Descriptive epidemiology study. Methods: Ankle injury data from the 2015-2016 through 2020-2021 NBA seasons were evaluated. The truncated 2019-2020 season due to the COVID-19 pandemic was omitted. The primary outcome was the incidence of ankle injuries, reported per 1000 game-exposures (GEs). Secondary analysis was performed to identify risk factors for ankle injuries through bivariate analysis and multivariable logistic regression of player demographic characteristics, performance statistics, injury characteristics, and previous lower extremity injuries. Factors influencing the time loss after injury were assessed via a negative binomial regression analysis. Results: A total of 554 ankle injuries (4.06 injuries per 1000 GEs) were sustained by NBA players over 5 NBA seasons, with sprain/strain the most common injury type (3.71 injuries per 1000 GEs). The majority of ankle injury events (55%) resulted in 2 to 10 game absences. The likelihood of sustaining an ankle injury was significantly associated with a greater number of games played ( P = .029) and previous injury to the hip, hamstring, or quadriceps ( P = .004). Increased length of absence due to ankle injury was associated with greater height ( P = .019), MPG ( P < .001), usage rate ( P = .025), points per game ( P = .011), and a prior history of foot ( P = .003), ankle ( P < .001), and knee injuries ( P < .001). Conclusion: The incidence of ankle injuries was 4.06 per 1000 GEs in professional basketball players. Games played and prior history of hip, hamstring, or quadriceps injuries were found to be risk factors for ankle injuries. Factors associated with physiologic burden such as MPG and usage rate were associated with an increased time loss after injury.

Abstract Background: The Ehlers-Danlos Syndromes (EDS) are a set of connective tissue disorders that are hereditary in nature and characterized by joint hypermobility and tissue fragility. The complex nature of this unique patient population requires multidisciplinary care, but appropriate centers for such care do not exist in large portions of the country. Need for more integrated services has been identified in the Chicagoland region. In order to explore and begin to address barriers to seeking out appropriate care facing EDS patients in this region, we developed an online survey which we circulated through EDS social media groups for Chicagoland patients. Results: Three hundred and nine unique respondents participated. We found that there exists a strong medical need for and interest in the development of a center in the region, and participants reported that, if made available to them, that they would make extensive and regular use of such a facility. Conclusions: We conclude that the establishment of a collaborative medical center specializing in the diagnosis and treatment of EDS, HSD, and related disorders in the Chicagoland area would greatly benefit patients by providing comprehensive care, alleviate the burden on overworked healthcare providers, and generate revenue for medical facilities.