Citations

Abstract Introduction: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 Chimeric Antigen Receptor (CAR) T-cell therapy that induces durable responses in patients with relapsed or refractory large B-cell lymphoma. At a median of 27.1 months follow-up on the ZUMA-1 trial, median overall survival (OS) was 25.8 months with 39% progression free survival (PFS) at 2 years post-infusion (Locke, Lancet Onc 2019). We previously reported outcomes of axi-cel patients treated with standard of care therapy at a median follow up of 12.9 months, including 42% who did not meet eligibility criteria for ZUMA-1 based on co-morbidities (Nastoupil, JCO 2020). Here we report results from this cohort at a median follow up of 32.4 months, as well as late outcomes of interest including cytopenias, infections and secondary malignancies. Methods and Results: The US Lymphoma CAR-T Consortium comprised of 17 US academic centers who contributed data independent of the manufacturer. Two hundred and ninety-eight patients underwent leukapheresis with intent to manufacture standard of care axi-cel as of September 30, 2018. In infused patients (n=275), OS and PFS were calculated from date of infusion. After median follow-up of 32.4 months (95% CI 31.1 - 34.3), median OS was not reached (95% CI 25.6 - not evaluable) (Figure 1A) with 1-, 2- and 3-year OS of 68.5% (95% CI 62.6-73.7), 56.4% (95% CI 50.1-62.2) and 52.2% (95% CI 45.7-58.2%), respectively. Median PFS was 9 months (95% CI 5.9-19.6) (Figure 1B); 1-, 2- and 3-year PFS was 47.4% (95% CI 41.4-53.2), 41.6% (95% CI 35.6-47.5) and 37.3% (95% CI 31.3-43.2), respectively. Twenty-seven PFS events occurred at or after 1 year post infusion;19 events were progressive lymphoma, with the latest relapse observed 28 months after axi-cel infusion. Eight patients died while in remission from their lymphoma: 4 from secondary malignancy, 3 from infection, and 1 from unknown causes. Results of multivariable modeling were similar to our prior analysis: factors associated with both a shorter PFS and shorter OS included male sex, elevated pre-lymphodepletion LDH, and poor ECOG status. Complete blood count and B- and T-cell recovery data were collected at 1 and 2-years post-infusion, excluding patients who had relapsed or been treated for secondary malignancy at time of collection (Table 1). Rates of neutropenia (absolute neutrophil count ≤1000) at 1- and 2- years were 9.2% (10/109) and 11.2% (9/80) and rates of CD4 count ≤200/ul were 62% (23/37) and 27% (7/26). Recovery of B cells was seen in 54% (15/28) and 57% (13/23) at 1-and 2-years post infusion. Infections were reported in 31.2% (34/109) patients between 6- and 12-months post infusion, and 17% (18/109) were severe, requiring either hospitalization and/or IV antibiotics. Twenty-one patients (24%, 21/89) had an infection between 1- and 2- years, 11% of which were severe. Twenty percent (10/49) of patients between 2- and 3-years had an infection and 4 (8%) were severe. Neutropenia, low CD4 counts, and IgG levels were not associated with infection, though patients with infection between 6-12 months were more likely to have received IVIG (p<0.001). No patient in this cohort died of COVID-19. Twenty-two of 275 (8%) patients were diagnosed with subsequent malignancy after axi-cel treatment: 14/275 (5%) patients were diagnosed with myeloid malignancies (MDS (n=12), AML (n=1), CMML (n=1)); other malignancies included squamous cell carcinoma of skin (n=3); sarcoma (n=1); endometrial (n=1); lung (n=1); mesothelioma (n=1) and AITL (n=1). Patients with myeloid malignancy had a median age of 62 at axi-cel apheresis (IQR 56-67), 64% were male and median lines of prior therapy was 4 (IQR 3-6), including 36% with a prior autologous stem cell transplant. Eleven patients were in remission from lymphoma at myeloid malignancy diagnosis, while 3 were diagnosed after progression and interval therapy. Conclusion: This multi-center retrospective study showed similar long-term results to the ZUMA-1 trial, despite including patients who did not meet ZUMA-1 eligibility criteria based on comorbidities. Sixteen percent of PFS events were seen after 1 year, largely due to disease progression. Late infection was common but was not explained by persistent neutropenia or low CD4 counts. Subsequent malignancy, including MDS, occurred in 8% of patients and require further study to better identify patients at risk. J.Y.S and M.D.J contributed equally; S.D and M.L contributed equally. Figure 1 Figure 1. Disclosures Jain: BMS, Kite/Gilead, Novartis, Precision Biosciences, Takeda: Consultancy. Nastoupil: Pfizer: Honoraria, Research Funding; MorphoSys: Honoraria; Takeda: Honoraria, Other: DSMC, Research Funding; ADC Therapeutics: Honoraria; IGM Biosciences: Research Funding; Genentech: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Gilead/Kite: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Denovo Pharma: Other: DSMC; Bayer: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding. Ghobadi: Atara: Consultancy; Amgen: Consultancy, Research Funding; Wugen: Consultancy; Celgene: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Lin: Gamida Cell: Consultancy; Juno: Consultancy; Merck: Research Funding; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Sorrento: Consultancy; Legend: Consultancy; Takeda: Research Funding; Vineti: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Reagan: Seagen: Research Funding; Kite, a Gilead Company: Consultancy; Genentech: Research Funding; Curis: Consultancy. Oluwole: Curio Science: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. McGuirk: EcoR1 Capital: Consultancy; Gamida Cell: Research Funding; Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Novartis: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astelllas Pharma: Research Funding; Pluristem Therapeutics: Research Funding; Fresenius Biotech: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding. Deol: Kite, a Gilead Company: Consultancy. Sehgal: Juno/Celgene: Research Funding; Kite/Gilead: Research Funding. Goy: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; LLC(Targeted Oncology): Consultancy; Xcenda: Consultancy, Honoraria; Xcenda: Consultancy; Acerta: Consultancy, Research Funding; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Hoffman la Roche: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Phamacyclics: Research Funding; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Michael J Hennessey Associates INC: Consultancy; Genentech/Hoffman la Roche: Research Funding; MorphoSys: Honoraria, Other; Karyopharm: Research Funding; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; Incyte: Honoraria; Medscape: Consultancy; Novartis: Consultancy, Honoraria; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Infinity/Verastem: Research Funding; Rosewell Park: Consultancy; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; OncLive Peer Exchange: Honoraria; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Constellation: Research Funding; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Hill: Pfizer: Consultancy, Honoraria; Beigene: Consultancy, Honoraria, Research Funding; Gentenech: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Celgene (BMS): Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Andreadis: CRISPR Therapeutics: Research Funding; GenMAB: Research Funding; Novartis: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Epizyme: Honoraria; Incyte: Honoraria; TG Therapeutics: Honoraria; Kite: Honoraria; Karyopharm: Honoraria; Atara: Consultancy, Honoraria; BMS: Research Funding; Merck: Research Funding. Muñoz: Seagen: Consultancy, Honoraria, Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Kite, a Gilead Company: Consultancy, Speakers Bureau; Pfizer: Consultancy; Janssen: Consultancy, Speakers Bureau; Juno/Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Alexion: Consultancy; BeiGene: Consultancy, Speakers Bureau; Fosunkite: Consultancy; Innovent: Consultancy; Debiopharma: Consultancy; Karyopharm: Consultancy; Genmab: Consultancy; ADC Therapeutics: Consultancy; Epizyme: Consultancy; Servier: Consultancy; Acrotech: Speakers Bureau; Verastem: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol Myers Squibb: Speakers Bureau; Genentech: Speakers Bureau; Aurobindo: Speakers Bureau; Physicians' Education Resource: Honoraria; Kyowa Kirin: Consultancy, Honoraria, Speakers Bureau; OncView: Honoraria; Targeted Oncology: Honoraria. Westin: AstraZeneca: Consultancy, Research Funding; 47 Inc: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Morphosys: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Umoja: Consultancy; Iksuda Therapeutics: Consultancy; MorphoSys: Consultancy, Research Funding; Curis: Research Funding; Genentech: Consultancy, Research Funding. Chavez: Bristol Myers Squibb: Speakers Bureau; Karyopharm Therapeutics: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Kite/Gilead: Consultancy; Abbvie: Consultancy; MorphoSys: Speakers Bureau; BeiGene: Speakers Bureau; Novartis: Consultancy; Adaptive: Research Funding; Epizyme: Speakers Bureau; AstraZeneca: Research Funding. Bennani: Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board; Vividion: Consultancy, Other: Advisory Board. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Miklos: Pharmacyclics: Patents & Royalties; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy; Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees. Locke: GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Umoja: Consultancy, Other; Cowen: Consultancy; EcoR1: Consultancy; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Legend Biotech: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role. Dahiya: Kite, a Gilead Company: Consultancy; Atara Biotherapeutics: Consultancy; Miltenyi Biotech: Research Funding; Jazz Pharmaceuticals: Research Funding; BMS: Consultancy. Lunning: Spectrum: Consultancy; AstraZeneca: Consultancy; Acrotech: Consultancy; Legend: Consultancy; Novartis: Consultancy; Kyowa Kirin: Consultancy; Karyopharm: Consultancy; Morphosys: Consultancy; TG Therapeutics: Consultancy; Janssen: Consultancy; AbbVie: Consultancy; Verastem: Consultancy; Myeloid Therapeutics: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; Daiichi-Sankyo: Consultancy; Beigene: Consultancy; ADC Therapeutics: Consultancy; Kite, a Gilead Company: Consultancy.

Abstract Background Cage implantations and autologous pelvic bone grafts are common surgical procedures to fuse the spine in cases of spinal disorders such as traumatic fractures or degenerative diseases. These surgical methods are designed to stably readjust the spine and to prevent late detrimental effects such as pain or increasing kyphosis. Benefits of these surgical interventions have been evaluated, but the long-term well-being of patients after the respective treatments has not yet been examined. This study was designed to evaluate the clinical outcome for patients who received iliac crest or cage implantations. Material and Methods Forty-six patients with traumatic fractures after they obtained an anterior fusion in the thoracic or lumbar spine (12 cages; mean age: 54.08 years; 34 pelvic bone grafts; mean age: 42.18 years) were asked to participate in the survey using a precast questionnaire according the Visual Analog Scale (VAS) Spine Score. Twenty-nine of them provided the data requested. Results Evaluation of the VAS scores of the patients, reporting at least 1 year after the surgery, revealed that cage implantations led to significantly better results with respect to all aspects of their daily life such as pain sensing, capability to undertake physical activities and exercise as compared with patients with autologous pelvic bone graft. Patients with autologous pelvic bone graft treatment reported a particularly poor overall satisfaction level concerning their long-term well-being. Conclusions Patients with cage implantation reported a higher degree of long-term well-being. The data provide evidence for a positive impact on the postsurgery quality of life after cage implantation.

Abstract Stroke-Like Migraine Attacks after Radiation Therapy (SMART) is a descriptive clinical entity consisting of transient hemispheric dysfunction. We were interested in pragmatic management patterns for patients with Recurrent Stroke-Like Episodes (R-SLE) of transient negative neurologic symptoms after cranial radiotherapy (RT) to define optimal management strategy and assess long-term outcomes. We conducted a retrospective review of all patients with recurrent negative neurologic symptoms after cranial RT who were treated at Mayo Clinic (Rochester), with follow-up extending until February 2021. Descriptive statistics and Chi-Square analysis was performed to assess for differences between patients with clinical cessation of symptoms, death, progressive encephalopathy and therapeutic class, patient and primary treatment characteristics (i.e. whole brain RT). We identified 27 patients with R-SLE after RT. 25 patients were included in analyses. Median age at diagnosis was 28.7 years (3.0-65.8 years, SD: 15.0 years). Median time from RT to symptom onset was 14.6 years (3.3-30.5 years, SD: 8.9 years). The most common presentations included hemiparesis (55.6%), hemisensory loss (22.2%), transient visual field loss (33.3%), encephalopathy (18.5%), and aphasia (22.2%). Antiseizure medications were most used for management of R-SLE (92%) followed by anti-platelets (68%), verapamil (52%), statins (48%), glucocorticoids (24%), antivirals (20%), and ACE inhibitors/angiotensin receptor blockers (16%). Beta blockers were not used. Verapamil use was frequently associated with clinical cessation of recurrent events with cessation being achieved in 64.7% of patients on verapamil versus 35.3% not on verapamil (p=0.0638). Other medical interventions did not approach clinical or statistical significance. Progressive encephalopathy was more common in patients without clinical cessation (87.5% vs. 23.5%, p=0.0026). All patients who died at last follow-up had progressive encephalopathy. We found cessation of recurrent negative neurologic symptoms after cranial RT in most patients. Verapamil use was associated with clinical cessation. Progressive encephalopathy was more common in patients without clinical cessation of recurrent events.

Abstract BACKGROUND Diffuse leptomeningeal glioneuronal tumor (DLGNT), also known as oligodendrogliomatosis, is a rare neuro-oncologic condition along the neuraxis that remains poorly understood in children. We sought to describe our institutional experience and quantitively summarize the clinical survival and prognostic features of DLGNT in the pediatric population across the contemporary literature. METHODS We report four institutional cases of pediatric DLGNT diagnosed between 2000-2020 based on retrospective review of our records, and performed a comprehensive literature search for published cases from 2000 onwards to create an integrated cohort for analysis. Kaplan-Meier estimations, Fisher’s exact test, and logistic regression were utilized to interrogate the data. RESULTS Our overall integrated cohort consisted of 54 pediatric DLGNT patients, with 19 (35%) female and 35 (65%) male patients diagnosed at an average age of 6.4 years (range, 1.3-17 years) by means of surgical biopsy. Chemotherapy was used in 45 cases (83%), and mean follow-up time of 54 months (range, 3-204). Across the entire cohort, overall survival 1 month after diagnosis was 96% (95% CI 86-99%), and by 10 years was 69% (95% CI 49-82%). On multivariate analysis of complete data, chemotherapy treatment (HR=0.23, P=0.04) was statistically predictive of longer overall survival. When including limited data, longer duration of symptoms by presentation (HR=1.03, P=0.03) was statistically predictive of shorter overall survival. CONCLUSIONS This is the first quantitative study of pediatric DLGNT clinical course. More than 2-out-of-3 pediatric DLGNT patients survive beyond one decade. Chemotherapy is statistically associated with longer survival in DLGNT pediatric patients and should form the core of any treatment regimen in this setting. Early detection by means of judicious imaging and surgical biopsy for tissue diagnosis can lead to earlier treatment and likely superior outcomes.

Background: Athletes of all sports often have shoulder instability, most commonly as anterior shoulder instability (ASI). For overhead athletes (OHAs) and those participating in throwing sports, clinical and surgical decision making can be difficult owing to a lack of long-term outcome studies in this population of athletes. Purpose/Hypothesis: To report presentation characteristics, pathology, treatment strategies, and outcomes of ASI in OHAs and throwers in a geographic cohort. We hypothesized that OHAs and throwers would have similar presenting characteristics, management strategies, and clinical outcomes but lower rates of return to play (RTP) when compared with non-OHAs (NOHAs) and nonthrowers, respectively. Study Design: Cohort study; Level of evidence, 3. Methods: An established geographic medical record system was used to identify OHAs diagnosed with ASI in the dominant shoulder. An overall 57 OHAs with ASI were matched 1:2 with 114 NOHAs with ASI. Of the OHAs, 40 were throwers. Sports considered overhead were volleyball, swimming, racquet sports, baseball, and softball, while baseball and softball composed the thrower subgroup. Records were reviewed for patient characteristics, type of sport, imaging findings, treatment strategies, and surgical details. Patients were contacted to collect Western Ontario Shoulder Instability index (WOSI) scores and RTP data. Statistical analysis compared throwers with nonthrowers and OHAs with NOHAs. Results: Four patients, 3 NOHAs and 1 thrower, were lost to follow-up at 6 months. Clinical follow-up for the remaining 167 patients (98%) was 11.9 ± 7.2 years (mean ± SD). Of the 171 patients included, an overall 41 (36%) NOHAs, 29 (51%) OHAs, and 22 (55%) throwers were able to be contacted for WOSI scores and RTP data. OHAs were more likely to initially present with subluxations (56%; P = .030). NOHAs were more likely to have dislocations (80%; P = .018). The number of instability events at presentation was similar. OHAs were more likely to undergo initial operative management. Differences in rates of recurrent instability were not significant after initial nonoperative management (NOHAs, 37.1% vs OHAs, 28.6% [ P = .331] and throwers, 21.2% [ P = .094]) and surgery (NOHAs, 20.5% vs OHAs, 13.0% [ P = .516] and throwers, 9.1% [ P = .662]). Rates of revision surgery were similar (NOHAs, 18.0% vs OHAs, 8.7% [ P = .464] and throwers, 18.2% [ P > .999]). RTP rates were 80.5% in NOHAs, as compared with 71.4% in OHAs ( P = .381) and 63.6% in throwers ( P = .143). Median WOSI scores were 40 for NOHAs, as compared with 28 in OHAs ( P = .425) and 28 in throwers ( P = .615). Conclusion: In a 1:2 matched comparison of general population athletes, throwers and OHAs were more likely to have more subtle instability, as evidenced by higher rates of subluxations rather than frank dislocations, when compared with NOHAs. Despite differences in presentation and the unique sport demands of OHAs, rates of recurrent instability and revision surgery were similar across groups. Similar outcomes in terms of RTP, level of RTP, and WOSI scores were achieved for OHAs and NOHAs, but these results must be interpreted with caution given the limited sample size.

Abstract Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age‐related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age‐related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony‐forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age‐appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.

AbstractEarly investigations into the magnetic resonance imaging (MRI) appearance of articular cartilage imaging relied on assessment of the morphology, with subsequent investigators reporting identifying increased T2 signal intensity, bright signal, in degenerated cartilage. The cartilage “black line sign” is a finding that has recently been described in the radiology literature to characterize cartilage pathology. This sign refers to a focal linear hypointense signal within articular cartilage that is oriented perpendicular to the subchondral bone on T2-weighted MRI. The diagnostic significance and clinical relevance of this sign is debated. Since its first description, several papers have further delineated the etiology, prevalence, and clinical relevance of these and other dark cartilage abnormalities. The intent of this article is to summarize these findings, with hopes of bringing to light the importance of dark cartilage lesions and their clinical implication in the world of knee surgery. We will briefly discuss the most probable etiologies of dark cartilage abnormalities and the major factors determining the unique signal intensity. The described anatomical patterns of this finding, the clinical importance, potential mimics, and current treatment recommendations will be reviewed.

Abstract The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process‐based measures and patient‐reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13‐member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha‐fetoprotein [AFP]) every 6 months, need for surveillance in high‐risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging‐Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high‐risk population.