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836 citation(s) found for "Stuart, MJ".

Consensus Statement for the Management and Treatment of Port-Wine Birthmarks in Sturge-Weber Syndrome
Sabeti, Sara , Ball, Karen L. , Burkhart, Craig N. , Eichenfield, Lawrence F. , Frieden, Ilona J. , Geronemus, Roy G. , Gupta, Deepti , Krakowski, Andrew C. , Levy, Moise L. , Metry, Denise W. , Nelson, J. Stuart , Tollefson, Megha M. , Kelly, Kristen M. , Kelly, Kristen M , Sabeti, Sara, Faith, Esteban Fernández

Mayo Clinic

JAMA Dermatology | November 11, 2020 | Volume: 157 | Issue: 1 | Pages: 98

10.1001/jamadermatol.2020.4226 | PMID 33175124 Get It

Investigating the Chronology of Meniscus Root Tears: Do Medial Meniscus Posterior Root Tears Cause Extrusion or the Other Way Around?
Krych, Aaron J. , LaPrade, Matthew D. , Rhodes, Nicholas G. , Johnson, Adam C. , Krych, Aaron J , Hevesi, Mario , Camp, Christopher L. , Stuart, Michael J.

Mayo Clinic

Orthopaedic Journal of Sports Medicine | November 4, 2020 | Volume: 8 | Issue: 11 | Pages: No page available

10.1177/2325967120961368 | PMID 33209944 Get It

Background: Meniscus root tears are increasingly being recognized. Meniscal extrusion has previously been associated with medial root tears; however, the relationship between secondary meniscal restraints, such as the meniscotibial (MT) ligament, extrusion, and root tears has yet to be formally evaluated. Purpose: To better understand the association between MT ligament competence, medial meniscal extrusion, and medial meniscus posterior root tears (MMPRTs) as well as to determine the progression of meniscal extrusion over time. Study Design: Case series; Level of evidence, 4. Methods: Serial magnetic resonance imaging (MRI) scans were reviewed for patients who showed evidence of medial meniscal extrusion and MMPRTs on at least 1 of ≥2 available MRI scans. All patients were symptomatic at the time of diagnosis. All MRI scans were analyzed independently by 2 board-certified musculoskeletal radiologists. MT ligament disruption, medial meniscal extrusion, and MMPRTs were recorded for each MRI scan. The time between MRI scans, presence of insufficiency fractures, and Outerbridge classification for the medial femur and tibia were also evaluated. Results: Overall, 27 knees in 26 patients were included in this study, with a total of 63 MRI scans analyzed (21 knees with 2 MRI scans, 3 with 3 MRI scans, and 3 with 4 MRI scans). All patients demonstrated clear medial meniscal extrusion and MT ligament disruption before the subsequent development of MMPRTs ( P < .001). Mean extrusion at the time of initial MRI was 3.3 ± 1.1 mm and increased significantly to 5.5 ± 1.8 mm at the time of first imaging with an identified MMPRT ( P < .001). The mean time between initial MRI and the first identification of an MMPRT on later MRI was 1.7 ± 1.6 years. Conclusion: In a sample of 27 symptomatic knees with serial MRI scans both before and after an MMPRT diagnosis, all patients demonstrated MT ligament disruption and associated meniscal extrusion before the development of subsequent medial meniscus root tears. These findings suggest that MT ligament disruption and medial meniscal extrusion represent early and predisposing events contributing to MMPRTs. Therefore, this provides a possible explanation of why meniscal extrusion is not corrected with medial meniscus root repair.
Cranial Radiation Can be Eliminated in Most Children with T-Cell Acute Lymphoblastic Leukemia (T-ALL) and Bortezomib Potentially Improves Survival in Children with T-Cell Lymphoblastic Lymphoma (T-LL): Results of Children's Oncology Group (COG) Trial AALL1
Chen, Zhiguo , Annett, Robert D. , Asselin, Barbara L. , Galardy, Paul J. , Harker‐Murray, Paul , Jaju, Alok , Lam, Allison, Miles, Rodney R., Okada, Maki , Patel, Samir , Schechter‐Finkelstein, Tal, Singh, Neelam, Steele, Amii C., Sulis, Maria Luisa , Vargas, Sarah , Wood, Charlotte, McKay, Patrick Zweider, Bollard, Catherine M. , Raetz, Elizabeth A. , Bollard, Catherine M , Teachey, David T. , Devidas, Meenakshi , Wood, Brent L. , Hayashi, Robert J. , August, Keith J. , Cho, Steve Y. , Dunsmore, Kimberly P , Fisher, Brian T. , Freedman, Jason Lawrence , Hermiston, Michelle L. , Horton, Terzah M. , Messinger, Yoav H. , Schafer, Eric S. , Shimano, Kristin A. , Winter, Stuart S. , Loh, Mignon L. , Hunger, Stephen P.

Mayo Clinic

Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 11-12

10.1182/blood-2020-134730 Get It

Background: The prognosis for patients (pts) with relapsed T-ALL and T-LL is dismal; the primary goal of T-ALL/T-LL treatment is to prevent relapse. AALL1231 was a COG phase 3 clinical trial that randomized children and young adults (age 1-30 years) to a modified augmented BFM (aBFM) backbone +/- the proteasome inhibitor bortezomib during induction and delayed intensification (DI) (1.3mg/m2 x 4 doses per block). Bortezomib was tested in frontline therapy based on strong preclinical data and data in relapse on COG AALL07P1. Pts were stratified as standard (SR), intermediate (IR), or very high risk (VHR), primarily based on disease response: morphologic and minimal residual disease (MRD) at end induction and end consolidation (T-ALL) and radiographic response (T-LL). To eliminate cranial radiation (CXRT) in all pts, (except VHR: Day 29 M3 marrow or EOC MRD &gt;0.1% or pts with overt CNS leukemia at diagnosis, CNS3), the aBFM backbone was modified to use dexamethasone (dex) as the sole corticosteroid and an extra pegaspargase dose was added in both induction and DI, following the MRC strategy. IR pts received a second interim maintenance (IM) phase (one Capizzi MTX; one HD-MTX). Following consolidation, VHR pts received 3 BFM high-risk intensification blocks in lieu of IM. Results: AALL1231 accrued 847 patients (824 eligible and evaluable) of 1400 anticipated from 2014 until early closure in 2017 when COG AALL0434 established that nelarabine (NEL) improved DFS in T-ALL (AALL1231 did not include NEL). The 3-year EFS for Arm A (no bortezomib) vs Arm B (bortezomib) were 81.7±2.4% and 85.1±2.2 % (HR=0.782, p=0.074) (3/31/20 data cut-off; see Table 1 for additional outcomes). SR and IR pts, who account for 95% of pts, had significantly improved EFS on Arm B as compared with Arm A. Yet, VHR patients had improved EFS on Arm A. Patients with T-LL had improved EFS and OS with bortezomib: 3-year EFS (76.5±5.9% vs 88.3±4.5%; p = 0.01); 3-year OS (78.0±5.8% vs 89.5±4.2%, p = 0.007). A similar improvement in EFS and OS was not seen in T-ALL; however, with longer follow-up this may change. No excess toxicity was seen on Arm B. A dex-based Induction did result in lower MRD rates; more T-ALL pts on AALL1231 had Day 29 MRD &lt;0.1% as compared with AALL0434 which used a prednisone-based Induction (AALL1231 Arm A: 69.6%; Arm B: 72.2%; AALL0434: 64.6%; p = 0.02). However, this did not translate into improved survival. Indeed OS, but not EFS was worse on AALL1231 than AALL0434. On-going analyses are investigating the increased mortality on AALL1231, but preliminary analyses suggest a combination of increased toxic deaths and overall poor outcome in the VHR group. On AALL0434, 90.8% of T-ALL pts received CXRT. On AALL1231, 9.5% of subjects were scheduled to receive CXRT (CNS3 T-ALL/T-LL: 5.7%; VHR T-ALL: 4.1%). A comparison of AALL0434 pts that received CXRT with similar AALL1231 pts not receiving CXRT on AALL1231 demonstrated similar EFS (p = 0.14) and OS (p = 0.42) (Table 2). CNS relapse rates were higher in these pts on AALL1231 (4.5%) as compared with AALL0434 (1.7%), but overall relapse rates were the same (6.5% vs 6.4%). Notably the benefit of NEL in AALL0434 was due to reduction of CNS relapses. 128 AALL1231 pts came off protocol therapy after the study was closed for physician or patient/parent choice. Data collection is underway to understand the reasons for removal, including if it was to receive NEL. Conclusions: Outcomes for SR and IR pts with T-ALL and T-LL treated with bortezomib were excellent despite the elimination of prophylactic CXRT. Bortezomib significantly improved 3-year EFS for these groups, comprising ~95% of pts. Outcomes for VHR pts were dismal and worse on the bortezomib arm. T-LL pts had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. This is the first trial to demonstrate an OS benefit for de novo pediatric T-LL with a new agent; however, longer follow-up is needed. Therapy intensification allowed elimination of CXRT in the majority of pts without excessive relapse. These results should be interpreted cautiously as the 3-yr OS on AALL1231 was inferior to AALL0434. Nevertheless, incorporating bortezomib into standard therapy for de novo T-LL appears advantageous. Future COG T-ALL/T-LLy trials will build on the positive findings from AALL0434 and AALL1231, balancing intensity while mitigating toxicity to maintain high cure rates without routine cranial radiation. (MLL, SPH, EAR contributed equally) Disclosures Teachey: Amgen: Consultancy; Janssen: Consultancy; La Roche: Consultancy; Sobi: Consultancy. Dunsmore:Dexcom: Current equity holder in publicly-traded company. Galardy:Abbott: Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company. Harker-Murray:Regerenon Pharmaceuticals: Consultancy. Hermiston:Sobi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Shimano:Novartis: Research Funding; Daiichi Sankyo: Research Funding; Pfizer: Research Funding; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. McKay:Immunogen: Current Employment. Bollard:Mana Therapeutics: Other: IP. Loh:Medisix Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Institutional Research Funding. Hunger:Novartis: Consultancy; Amgen Inc.: Current equity holder in publicly-traded company, Honoraria. Raetz:Celgene/BMS: Other; Pfizer: Research Funding. OffLabel Disclosure: Bortezomib for the treatment of acute lymphoblastic leukemia under an IND
Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not
Nath, Rajneesh , Choe, Hannah , Seropian, Stuart , Stiff, Patrick J. , Abhyankar, Sunil , Agura, Edward, Litzow, Mark R. , Tomlinson, Benjamin , Orozco, Johnnie J. , Al‐Kadhimi, Zaid , Abboud, Camille N. , Magalhaes-Silverman, Margarida Magalhaes, Foran, James M. , Schuster, Michael W., Levy, Moshe , Liang, Qing , Berger, Mark S., Reddy, Vijay , Pagel, John M. , Gyurkocza, Boglarka , Chen, George L. , Hari, Parameswaran , Besien, Koen van , Sabloff, Mitchell , Magalhaes‐Silverman, Margarida , Kebriaei, Partow , Lazarus, Hillard M. , Giralt, Sergio

Mayo Clinic

Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 42-44

10.1182/blood-2020-134948 Get It

Background: Patients ≥55 years of age with high-risk acute myeloid leukemia (AML) may benefit from an allogeneic hematopoietic cell transplantation (HCT), which is often the only potentially curative therapy available. However, complete remission (CR) is usually a pre-requisite for most centers to perform HCT, as CR predicts an optimal outcome. Many older patients with relapsed/refractory (R/R) AML are not transplanted as they do not achieve the required CR. In addition, due to their advanced age, they are unable to tolerate the myeloablative conditioning required for eradication of disease, while the more tolerable reduced intensity conditioning often exhibits high rates of relapse. The SIERRA trial is a prospective, randomized, phase 3 trial for older patients with R/R AML to address this unmet need. We hypothesized that a targeted delivery of radiation to the marrow, achieved with a limit of 24 Gray (Gy) radiation dose to the liver, via an infusion of a therapeutic dose of Iomab-B enables successful engraftment despite active disease in the marrow. Methods: Eligible patients were ≥55 years with active R/R AML (≥5% blasts), adequate organ function, and related/unrelated 8/8 HLA-matched donors. Patients were randomized (1:1) to the Iomab-B or Conventional Care (CC) arm. Patients randomized to Iomab-B received an outpatient dosimetric dose of Iomab-B followed by nuclear medicine imaging to determine the personalized therapeutic dose that would deliver radiation to the marrow while limiting the delivery of radiation to the liver to 24 Gy. HCT is performed 12-14 days following the infusion of a therapeutic dose of Iomab-B, and a non-myeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and low-dose Total Body Irradiation (TBI 2 Gy x 1 dose). Patients on the CC arm received investigator's choice of salvage therapy, including newly approved targeted agents, and could proceed to physician's choice of conditioning and HCT if they achieved CR. If CC patients did not achieve CR, the study allowed them to cross-over and receive Iomab-B-based conditioning followed by allogeneic HCT. Results: Preliminary data were available from 106 patients (Table 1). 53 patients (median age 64) were randomized to Iomab-B and received allogeneic transplant. All Iomab-B patients engrafted, despite a pre-therapy median of 26% marrow blasts. After randomization, 83% (44/53) CC patients failed salvage therapy, including 45% (24/53) who received targeted agents. 26 of 44 (60%) CC patients, with a median 33% marrow blasts, crossed over and received Iomab-B followed by allogeneic HCT. Patient age, donor type (MRD, MUD), bone marrow cellularity, blast percentage, type of donor, stem cell dose, administered Iomab-B activity (mCi), and absorbed radiation dose to the marrow (Gy), were analyzed for time to engraftment among each group. Median time to neutrophil and platelet engraftment were 14 days (range 9-22) and 17 days (range 4-39) respectively, with 91% of evaluable patients achieving full donor chimerism (&gt;95% by day 100, Table 1). Neither the radiation dose delivered to the marrow (median 14.7 Gy; range, 4.6-32 Gy; Table 1) nor the total administered activity (median 632 mCi; range, 354-1027 mCi) showed correlation with the time to either neutrophil (p value=0.525) or platelet engraftment (p value=0.952). Regression analyses, considering all of the variables individually, did not indicate a statistically significant correlation (p &gt; 0.1) between days to engraftment and radiation dose delivered to the marrow. These results were consistent for the Iomab-B cross-over group as well. Furthermore, the marrow absorbed dose did not show a significant correlation with % chimerism at day 28 in patients on the Iomab-B arm or in cross-over patients. Conclusion: Dosimetry to determine a patient-specific therapeutic dose of Iomab-B of 24 Gy to the liver provided absorbed marrow radiation doses that allowed for reliable engraftment after allogeneic HCT in older patients with R/R AML, despite a heavy leukemia burden with median bone marrow blasts of 26% prior to HCT (Iomab-B arm). There was no relationship between total administered activity or radiation dose delivered to the marrow with the speed of engraftment. The SIERRA trial is currently enrolling patients (www.sierratrial.com or clinicaltrials.gov NCT02665065). Disclosures Gyurkocza: Actinium: Research Funding. Nath:Daiichi Sankyo: Consultancy, Honoraria; Actinium: Consultancy, Honoraria; Astellas: Consultancy, Honoraria. Stiff:Kite, a Gilead Company: Research Funding; Gamida Cell: Research Funding; Atara: Research Funding; Unum: Research Funding; Macrogenics: Research Funding; Delta-Fly: Research Funding; Amgen: Research Funding. Hari:Takeda: Consultancy; BMS: Consultancy; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Incyte Corporation: Consultancy. Al-Kadhimi:Actinium Pharmaceuticals Inc.: Research Funding; Genzyme: Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; Gilead Science: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Novavax: Current equity holder in publicly-traded company. Abboud:BMS: Current equity holder in publicly-traded company; AbbVie Inc: Current equity holder in publicly-traded company; Forty Seven Inc: Research Funding; Abbott Labs: Current equity holder in publicly-traded company; AlloVir: Research Funding; Ryvu: Research Funding; Actinium Pharmaceuticals Inc.: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; Pfizer: Research Funding. Magalhaes-Silverman:Incyte: Research Funding; Kadmon Holdings: Research Funding; Actinium Pharmaceuticals: Research Funding. Foran:BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding; Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; Revolution Medicine: Consultancy; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Schuster:Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Takeda, Genentech,, Seattle Genetics: Other: Personal Fees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Ziopharm: Other: Research Support; Jazz: Consultancy; Novartis: Other: Served on advisory board; Kite: Other: Served on advisory board. Levy:Karyopharm: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Research Funding, Speakers Bureau; Baylor University Med Center: Current Employment. Giralt:ACTINUUM: Consultancy, Research Funding; MILTENYI: Consultancy, Research Funding; KITE: Consultancy; TAKEDA: Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria; AMGEN: Consultancy, Research Funding; OMEROS: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria, Research Funding. Liang:Actinium Pharmaceuticals: Current Employment. Berger:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company. Reddy:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company.
High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acu
Nath, Rajneesh , Choe, Hannah , Seropian, Stuart , Stiff, Patrick J. , Abhyankar, Sunil , Agura, Edward, Litzow, Mark R. , Tomlinson, Benjamin , Orozco, Johnnie J. , Al‐Kadhimi, Zaid , Abboud, Camille N. , Magalhaes-Silverman, Margarida Magalhaes, Foran, James M. , Schuster, Michael W., Levy, Moshe , Liang, Qing , Berger, Mark S., Reddy, Vijay , Pagel, John M. , Gyurkocza, Boglarka , Chen, George L. , Hari, Parameswaran , Besien, Koen van , Sabloff, Mitchell , Magalhaes‐Silverman, Margarida , Kebriaei, Partow , Lazarus, Hillard M. , Giralt, Sergio

Mayo Clinic

Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 30-31

10.1182/blood-2020-134624 Get It

Background: Despite recently approved novel targeted therapies, most patients with high-risk acute myeloid leukemia (AML) still require allogeneic hematopoietic cell transplantation (HCT) to achieve long-term survival. However, older patients with relapsed/refractory (R/R) AML are often unable to undergo HCT due to the toxicity of myeloablative pre-conditioning. Since higher doses of chemotherapy and radiation are associated with prolonged myelosuppression or infectious complications, targeted radiotherapy with Iomab-B, employed in the SIERRA trial, was designed to minimize toxicities in a patient population unable to tolerate standard high-dose myeloablative HCT pre-conditioning. We hypothesize that Iomab-B, which spares non-hematologic organs such as the GI tract, exhibits a favorable toxicity profile with respect to mucositis, febrile neutropenia (FN), and sepsis. Methods: The SIERRA trial is a prospective trial for patients ≥55 years of age with R/R AML (≥5% blasts) and 8/8 HLA-matched related or unrelated donors. Patients were randomized (1:1) to Iomab-B or Conventional Care (CC). Those in the Iomab-B group received a dosimetric infusion of Iomab-B followed by nuclear imaging to determine the personalized therapeutic dose to be delivered to the bone marrow and to other sites of disease. Therapeutic dose calculations, utilizing the Olinda software (Version 2.1, Hermes Medical) to determine the delivery of a maximum of 24 Gray (Gy) dose to the liver, were performed based on the imaging results. HCT is performed 12-14 days following the infusion of a therapeutic dose of Iomab-B, and a non-myeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and low-dose Total Body Irradiation (TBI 2 Gy x 1 dose). CC patients received the investigator's choice of salvage therapy. Safety data was evaluated from randomization and up to 100 days after HCT in the patients randomized to the Iomab-B group. We specifically evaluated AE variables of mucositis (Gr 2-4), FN (Gr3,4) and sepsis. An analysis was performed with both total activity of Iomab-B as well as with the radiation dose delivered to the bone marrow, stomach wall, small and large intestinal walls. For each of the 3 AEs of interest, a multivariate analysis was performed, allowing each of the predictor variables to be included in the model. Results: A total of 106 patients were randomized at the time of analysis. For those randomized to Iomab-B, data is available for 45 patients that received a therapeutic dose of Iomab-B and HCT. The median dose of Iomab-B administered was 603 mCi (range 313-1027 mCi) and the median radiation dose delivered to the marrow in the Iomab-B group was 14.7 Gy (range 4.6 - 32 Gy). All patients (median age 64) treated with a therapeutic dose of Iomab-B achieved neutrophil engraftment after a median of 14 days post-HCT (range 9-22), despite presenting with a median 26% marrow blasts prior to initiation of therapy. Rates of mucositis, FN, and sepsis are shown in Table 1. No correlation between AEs (FN, mucositis, sepsis) and administered Iomab-B activity (p=0.08), nor with dose delivered to GI tract (p=0.09) was observed. Furthermore, these AEs were not related to the dose of radiation received by the small intestine (median 2.7 Gy range 1.1-6.8 Gy) large intestine (median 2.6 Gy range 0.9-6.5 Gy), nor an average of all 4 GI sites (median 2.8 Gy range 1.6-6.8 Gy). Conclusions: Unlike cases involving treatment with cytotoxic chemotherapy and external beam radiation where mucositis, infections and sepsis increase along with the administered dose, targeted myeloablative conditioning with Iomab-B resulted in low incidences of severe mucositis, FN, and sepsis. These AEs do not appear to be related to the total dose of Iomab-B administered nor to the specific radiation dose delivered to the bone marrow. Furthermore, a low dose of radiation (2.8 Gy) was received by the GI tract compared to the larger dose of radiation (14.7 Gy) delivered to the marrow. Taken together, these results represent potentially significant improvements in the safe delivery of myeloablative therapy with high-dose targeted radioimmunotherapy, prior to HCT in older patients with R/R AML. This SIERRA trial is currently enrolling patients (www.sierratrial.com or clinicaltrials.gov NCT02665065). Disclosures Gyurkocza: Actinium: Research Funding. Nath:Actinium: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria. Stiff:Kite, a Gilead Company: Research Funding; Gamida Cell: Research Funding; Atara: Research Funding; Unum: Research Funding; Delta-Fly: Research Funding; Macrogenics: Research Funding; Amgen: Research Funding. Hari:Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; BMS: Consultancy; Takeda: Consultancy; Incyte Corporation: Consultancy. Al-Kadhimi:Actinium Pharmaceuticals Inc.: Research Funding; Genzyme: Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; Gilead Science: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Novavax: Current equity holder in publicly-traded company. Abboud:Ryvu: Research Funding; Actinium Pharmaceuticals Inc.: Research Funding; Pfizer: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company; Abbott Labs: Current equity holder in publicly-traded company; AbbVie Inc: Current equity holder in publicly-traded company; AlloVir: Research Funding; Forty Seven Inc: Research Funding. Magalhaes-Silverman:Kadmon Holdings: Research Funding; Actinium Pharmaceuticals: Research Funding; Incyte: Research Funding. Foran:Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy; Agios: Honoraria, Research Funding; H3Biosciences: Research Funding. Schuster:Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Takeda, Genentech,, Seattle Genetics: Other: Personal Fees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Amgen: Other: Research Support; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Jazz: Consultancy. Levy:Karyopharm,Takeda, BMS: Consultancy, Honoraria, Speakers Bureau. Giralt:KITE: Consultancy; NOVARTIS: Consultancy, Honoraria, Research Funding; OMEROS: Consultancy, Honoraria; ACTINUUM: Consultancy, Research Funding; MILTENYI: Consultancy, Research Funding; TAKEDA: Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria; AMGEN: Consultancy, Research Funding. Liang:Actinium Pharmaceuticals: Current Employment. Berger:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company. Reddy:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company.
Quantitative REM Sleep without Atonia in Parkinson's Disease and Essential Tremor
Gossard, Thomas , McCarter, Stuart J. , Gorres, E., Feemster, John, Timm, Paul, Teigen, Luke, Ralston, Christy L., Westerland, Sarah M., Conway, Jimmy P., Jagielski, Jack T. , Olson, Carl D., Edgar, Liam J., Veum, Emma L., Savica, Rodolfo , Silber, Michael H. , Louis, Erik K. St. , Boeve, Brad F, St Louis, E K , Gossard, Thomas R , Jagielski, Jack , McCarter, Stuart J , Boeve, Bradley F.

Mayo Clinic

Movement Disorders Clinical Practice | November 2, 2020 | Volume: 8 | Issue: 1 | Pages: 37-43

10.1002/mdc3.13112 | PMID 33426157 Get It

ABSTRACTBackgroundRapid eye movement (REM) sleep behavior disorder (RBD) occurs occasionally in essential tremor (ET), but polysomnographic REM sleep without atonia (RSWA) analyses have been sparse.ObjectiveTo characterize the amount and distribution of polysomnographic RSWA, the electrophysiologic substrate of RBD, in patients with Parkinson's disease (PD) and ET.MethodsWe analyzed quantitative RSWA in 73 patients: PD (23), ET (23), and age‐sex‐matched controls (27). None had dream‐enactment behavior history or received antidepressants. Phasic, tonic, “any,” and phasic‐burst duration RSWA measures were calculated in the submentalis (SM) and anterior tibialis (AT) muscles. The automated REM atonia index (RAI) was also determined. Statistical analysis was performed by Kruskal‐Wallis rank‐sum and Mann‐Whitney tests.ResultsSM phasic RSWA was significantly greater for PD than ET patients and controls (12.5% ± 12.8% vs. 4.9% ± 6.7%, 3.9% ± 2.6%), as was SM “any” (13.54% ± 14.30% vs. 5.2% ± 7.6%, 4.2% ± 2.6%). RAI was significantly lower in PD than in ET and controls (0.78 ± 0.23 vs. 0.92 ± 0.09 vs. 0.90 ± 0.17, P ≤ 0.005), but no different between ET and controls. AT phasic and “any” RSWA was similar between the 3 groups. ET and control RSWA was similar in all measures. Two ET patients (8.7%) had SM RSWA similar to PD patients.ConclusionsElevated SM RSWA distinguished PD from ET in patients without dream‐enactment symptoms and occurs frequently in PD patients, and in isolated tremor suggests underlying synucleinopathy. Prospective studies will further validate these findings.
Hamstring Autograft Anterior Cruciate Ligament Reconstruction Using an All‐Inside Technique With and Without Independent Suture Tape Reinforcement
Parkes, Chad W. , Leland, Devin P. , Levy, Bruce A. , Saris, Daniël B.F. , Krych, Aaron J. , Krych, Aaron J , Stuart, Michael J. , Camp, Christopher L.

Mayo Clinic

Arthroscopy | November 2, 2020 | Volume: 37 | Issue: 2 | Pages: 609-616

10.1016/j.arthro.2020.09.002 | PMID 33144236 Get It

Purpose To compare the (1) rates of complications and reoperations, (2) rate of anterior cruciate ligament (ACL) graft failure, and (3) patient‐reported outcomes (PROs) among patients after hamstring autograft ACL reconstruction (ACLR) with and without independent suture tape reinforcement at a minimum 2‐year clinical follow‐up. Methods We performed a 1:2 matched‐cohort comparison of patients who underwent hamstring autograft ACLR with and without independent suture tape reinforcement between July 2011 and July 2017. Patients were matched according to age, sex, body mass index, preinjury Tegner activity score, and concomitant meniscal injury. Medical records were reviewed for demographic characteristics, additional injuries, and concomitant procedures. PRO scores (including Tegner activity, Lysholm, and International Knee Documentation Committee scores) and physical examination findings were collected both preoperatively and at a minimum of 2 years postoperatively. Results Overall, 108 patients who underwent ACLR were included: 36 patients (mean age, 25.3 years; range, 13‐44 years) with independent suture tape reinforcement and 72 patients (mean age, 24.9 years; range, 13‐54 years) without suture tape reinforcement. Overall, 5 of 36 suture tape patients (14%) and 10 of 72 control patients (14%) underwent reoperations. At an average follow‐up of 26.1 months in the suture tape cohort and 31.3 months in the control cohort, 1 patient in the suture tape cohort and 4 patients in the control cohort experienced graft failure. There were no statistically significant differences between the suture tape and control groups regarding return‐to‐sport rate (89% and 88%, respectively), postoperative International Knee Documentation Committee score (94.4 and 93.8, respectively), and postoperative Lysholm score (95.6 and 94, respectively). There was a statistically significant difference between the suture tape and control groups in postoperative Tegner activity score, at 7.1 (95% confidence interval, 6.5‐7.6) and 6.4 (95% confidence interval, 6.2‐6.6), respectively ( P = .026). Conclusions ACLR with hamstring autograft and independent suture tape reinforcement was performed safely with low rates of complications, graft failure, and reoperations with similar PROs, function, and return‐to‐sport rates when compared with hamstring autograft ACLR without suture tape reinforcement at a minimum 2‐year follow‐up. Level of Evidence Level III, retrospective comparative study.
Small Cartilage Defect Management
Hacken, Brittney , LaPrade, Matthew D. , Stuart, Michael J. , Saris, Daniël B.F. , Krych, Aaron J. , Hacken, Brittney A, Krych, Aaron J , Stuart, Michael J , Camp, Christopher L.

Mayo Clinic

The Journal of Knee Surgery | October 6, 2020 | Volume: 33 | Issue: 12 | Pages: 1180-1186

10.1055/s-0040-1716359 | PMID 32898908 Get It

AbstractCartilage defects in the knee are common resulting in significant pain and morbidity over time. These defects can arise in isolation or concurrently with other associated injuries to the knee. The treatment of small (< 2–3 cm2) cartilage deficiencies has changed as our basic science knowledge of tissue healing has improved. Advancements have led to the development of new and more effective treatment modalities. It is important to address any associated knee injuries and limb malalignment. Surgical options are considered when nonoperative treatment fails. The specific procedure depends on individual patient characteristics, lesion size, and location. Debridement/chondroplasty, microfracture, marrow stimulation plus techniques, fixation of unstable osteochondral fragments, osteochondral autograft transfer, and osteochondral allograft transplantation, all have roles in the treatment of small cartilage defects.
Diagnosis and Treatment of Femoral Head Osteonecrosis: A Protocol for Development of Evidence Based Clinical Practice Guidelines
Cheng, Edward Y. , Mont, Michael A. , Cui, Quanjun , Salem, Hytham S. , Bakker, Caitlin , Sugano, Nobuhiko , Goodman, Stuart B. , Sierra, Rafael J.

Mayo Clinic

No container title available | October 1, 2020 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-77450/v1 Get It

Abstract Background: There are many treatment options for patients who have osteonecrosis of the femoral head (ONFH) and management strategies vary widely both among and within individual countries. Although many researchers have attempted to elucidate the optimal strategies for managing this disease, the lack of large-scale randomized control trials and the lack of agreement on disease staging have curtailed the development of clear-cut guidelines.Methods: The Association Research Circulation Osseous (ARCO) group sought to address three questions for the management of patients who have ONFH: (1) What imaging studies are most sensitive and specific for the diagnostic evaluation of patients who have ONFH?; (2)What is the best treatment strategy for preventing disease progression in patients who have pre-collapse lesions?; and (3) What is the best treatment strategy for patients who have post-collapse disease? The PICO (Patient, Intervention, Comparison, and Outcome) format was used to formulate the search strategy for each research question. A systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ARCO participants have been allocated to three groups, each representing one of the PICO questions. After qualitative and quantitative analysis of the data extracted from studies pertaining to each of the three research questions, a set of evidence-based clinical practice guidelines will be proposed for the management of patients who have ONFH. Discussion: It is not always clear which treatment method is optimal for the management of ONFH. Thus, many surgeons have developed and performed various procedures based on various patient-specific factors. As there is no consensus on the optimal treatment for various stages of disease, it was clear that developing evidence-based clinical practice guidelines would provide more structure and uniformity to management of these patients. Therefore, the results of this systematic review will lead to the development guidelines that may improve patient-care strategies and result in better outcomes for patients who have ONFH.Systematic Review Registration: Registration with PROSPERO has been submitted and is pending.