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Objectives: The sensitivity and specificity of clot lysis at 30 minutes after maximum clot strength (LY30), as measured by thromboelastography (TEG), for clinically significant hyperfibrinolysis have not been compared across the 2 US Food and Drug Administration-approved instruments (the TEG 5000 and TEG 6s [Haemonetics])., Methods: We performed a retrospective, single-center analysis of these 2 instruments using the kaolin (CK) reagent., Results: Local verification studies showed that the TEG 5000 and TEG 6s CK LY30 upper limits of normal (ULNs) were distinct (5.0% and 3.2%, respectively). Retrospective analysis of patient data showed that abnormal LY30 was 6 times more prevalent with the TEG 6s than with the TEG 5000 instrument. LY30 was a significant predictor of mortality with both instruments (TEG 6s: receiver operating characteristic [ROC] area under the curve [AUC] = 0.836, P ≤ .0001; TEG 5000: ROC AUC = 0.779, P = .028). The optimal LY30 cut point was determined based on these mortality data for each instrument. The TEG 6s showed superior mortality prediction than the TEG 5000 at lower LY30 levels (≥10%), with likelihood ratios of 8.22 and 2.62 for the TEG 6s and TEG 5000, respectively. Patients with a TEG 6s CK LY30 of 10% or higher were significantly more likely to die, receive cryoprecipitate, receive transfusions, or receive massive transfusion than patients with a TEG 6s LY30 of 3.3% to 9.9% (all P < .01). Patients with a TEG 5000 LY30 of 17.1% or higher were significantly more likely to die or use cryoprecipitate (P < .05); transfusion and massive transfusion protocol were not significantly different. Whole blood spiking studies showed that 70 ng/mL tissue plasminogen activator (tPA) achieved an average LY30 of approximately 10% for both instruments., Conclusions: CK LY30 above the ULN is a sensitive but not specific cutoff for hyperfibrinolysis. At least moderately elevated CK LY30 carries more clinical portent on the TEG 6s instrument than on the TEG 5000. These TEG instruments are not sensitive to low concentrations of tPA., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sickle cell disease is a lifelong disorder which may be managed by chronic red cell transfusion including exchange transfusion. Chronic indwelling vascular catheters including ports offer convenient and reliable access for red cell exchange but confer risk of complications including infection and thrombosis. Detection of these complications is essential for preserving vascular access and relies on both clinical and laboratory observation. Here we describe a case of asymptomatic port infection detected by manual screening of a peripheral blood smear., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Combination of antiprogrammed cell death protein-1 (PD-1) plus anti-cytotoxic T-cell lymphocyte-4 (anti-CTLA-4) immunotherapy shows greater response rates (RRs) than anti-PD-1 antibody alone in melanoma, but RR after initial anti-PD-1 and programmed death ligand-1 (PD-L1) antibody progression awaits robust investigation. Anti-CTLA-4 antibody alone after anti-PD-1/L1 antibody progression has a historical RR of 13%. We report the results of the first prospective clinical trial evaluating ipilimumab 1 mg/kg plus pembrolizumab following progression on anti-PD-1 immunotherapy., Methods: Patients with advanced melanoma who had progressed on anti-PD-1/L1 antibody as immediate prior therapy (including non-anti-CTLA-4 antibody combinations) were eligible. Patients received pembrolizumab 200 mg plus ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by pembrolizumab monotherapy. The primary end point was RR by irRECIST. After 35 patients, the trial met the primary end point and was expanded to enroll a total of 70 patients to better estimate the RR., Results: Prior treatments included 60 on anti-PD-1 antibody alone and 10 on anti-PD-1/L1 antibody-based combinations. Thirteen patients had progressed in the adjuvant setting. The median length of prior treatment with anti-PD-1/L1 antibody was 4.8 months. Response assessments included five complete and 15 partial responses, making the irRECIST RR 29% among the entire trial population. The median progression-free survival was 5.0 months, and the median overall survival was 24.7 months. The median duration of response was 16.6 months. There was no difference in median time on prior anti-PD1/L1 or time to PD1 + CTLA4 initiation between responders and nonresponders. Grade 3-4 drug-related adverse events occurred in 27% of patients. Responses occurred in PD-L1-negative, non-T-cell-inflamed, and intermediate tumor phenotypes., Conclusion: To our knowledge, this is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability., Competing Interests: Zeynep ErogluConsulting or Advisory Role: Regeneron, Sun Pharma, Genentech/Roche, Novartis, OncoSec, Natera, ElsevierResearch Funding: Novartis, Pfizer Bruce BrocksteinConsulting or Advisory Role: Exelixis/IpsenResearch Funding: AstraZenecaPatents, Royalties, Other Intellectual Property: UpToDate. Author and Editorial duties Andrew S. PoklepovicConsulting or Advisory Role: NovartisSpeakers' Bureau: Bristol Myers Squibb Sunil BabuEmployment: Fort Wayne Medical Oncology & HematologyStock and Other Ownership Interests: Fort Wayne Medical Oncology & Hematology, Lutheran HospitalHonoraria: Bristol Myers Squibb, Alexion Pharmaceuticals, Lilly, Bayer, AstraZenecaConsulting or Advisory Role: Bristol Myers Squibb, Alexion Pharmaceuticals, AstraZeneca, argenx, Boehringer Ingelheim, Bayer, Kite, a Gilead company, Janssen Oncology, AmgenSpeakers' Bureau: Alexion PharmaceuticalsResearch Funding: Bristol Myers Squibb, Novartis, Genentech/Roche, AstraZeneca/MedImmune, Janssen Oncology, Amgen, TG Therapeutics, Abbvie, Lilly, Alexion Pharmaceuticals, Merck, Novartis, Syndax, Nektar, Sanofi, argenxTravel, Accommodations, Expenses: Bristol Myers Squibb, Alexion Pharmaceuticals, Lilly, Janssen Oncology, Genentech/Roche Sigrun HallmeyerLeadership: Association of Community Cancer Centers (ACCC)Honoraria: Cardinal HealthConsulting or Advisory Role: Bristol Myers Squibb, Cardinal Health, Array PharamceuticalSpeakers' Bureau: Bristol Myers SquibbTravel, Accommodations, Expenses: Cardinal Health, Bristol Myers SquibbUncompensated Relationships: Society for Immunotherapy of Cancer Mario VelascoEmployment: Cancer Care Specialists of IL Jose LutzkyConsulting or Advisory Role: Castle Biosciences, Iovance Biotherapeutics, Replimune, RegeneronResearch Funding: Bristol Myers Squibb, Novartis, Iovance Biotherapeutics, Immunocore, Regeneron, Replimune, Vyriad Emily HiggsEmployment: LillyStock and Other Ownership Interests: LillyResearch Funding: LillyPatents, Royalties, Other Intellectual Property: Jeffrey D. Helterbrand, Richard E. Higgs, Phillip W. Iversen, Automatic Contextual Segmentation for Imaging Bones for Osteoporosis Therapies (Granted February 1, 2000, US Patent 6,021,213). Raymond E. Kaiser, Richard E. Higgs, Randall K. Julian Jr, System and Methods for Quantitatively Comparing Complex Mixtures Using Single Ion Chromatograms Derived From Spectroscopic Analysis of Such Admixtures (Granted March 23, 1999, US Patent 5,885,841)Travel, Accommodations, Expenses: Lilly Vernon K. SondakConsulting or Advisory Role: Merck/Schering Plough, Novartis, Bristol Myers Squibb, Regeneron, Replimune, EisaiTravel, Accommodations, Expenses: Polynoma, Merck, Bristol Myers Squibb, Replimune Thomas F. GajewskiStock and Other Ownership Interests: Jounce Therapeutics, Evelo Therapeutics, Five Prime Therapeutics, PyxisConsulting or Advisory Role: Merck, Jounce Therapeutics, Adaptimmune, FOGPharma, Allogene Therapeutics, Pyxis, Trillium Therapeutics, Janssen Oncology, Gilead SciencesResearch Funding: Bristol Myers Squibb, Merck, Roche/Genentech, Incyte, Seattle Genetics, Ono Pharmaceutical, Aduro Biotech, Pyxis, BayerPatents, Royalties, Other Intellectual Property: Licensing to Evelo, Licensing to Aduro, Licensing to BMS, Licensing to Pyxis Nikhil I. KhushalaniStock and Other Ownership Interests: Bellicum Pharmaceuticals, Mazor Robotics, Amarin Corporation, Asensus SurgicalHonoraria: SanofiConsulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Regeneron, Array BioPharma, Immunocore, Merck, Incyte, Jounce Therapeutics, Iovance Biotherapeutics, NCCN/PfizerResearch Funding: Bristol Myers Squibb, Merck, Novartis, GlaxoSmithKline, HUYA Bioscience International, Amgen, Regeneron, Celgene, Replimune Jason J. LukeStock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch OncologyConsulting or Advisory Role: Array BioPharma, Bristol Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, TTC Oncology, Alphamab, Compugen, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf Therapeutics, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius Therapeutics, Tesaro, Xilio Therapeutics, XencorResearch Funding: Merck, Bristol Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Checkmate Pharmaceuticals, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma, EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring Bank, Trishula TherapeuticsPatents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)Travel, Accommodations, Expenses: Bristol Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio TherapeuticsNo other potential conflicts of interest were reported.

Importance: Clinical trial registries are intended to increase clinical research transparency by nonselectively identifying and documenting clinical trial designs and outcomes. Inconsistencies in reported data undermine the utility of such registries and have previously been noted in general medical literature., Objective: To assess whether inconsistencies in reported data exist between ophthalmic literature and clinical trial registries., Design, Setting, and Participants: In this retrospective, cross-sectional study, interventional clinical trials published from January 1, 2014, to December 31, 2014, in the American Journal of Ophthalmology, JAMA Ophthalmology, and Ophthalmology were reviewed. Observational, retrospective, uncontrolled, and post hoc reports were excluded, yielding a sample size of 106 articles. Data collection was performed from January through September 2016. Data review and adjudication continued through January 2017., Main Outcomes and Measures: If possible, articles were matched to registry entries listed in the ClinicalTrials.gov database or in 1 of 16 international registries indexed by the World Health Organization International Clinical Trials Registry Platform version 3.2 search engine. Each article-registry pair was assessed for inconsistencies in design, results, and funding (each of which was further divided into subcategories) by 2 reviewers and adjudicated by a third., Results: Of 106 trials that met the study criteria, matching registry entries were found for 68 (64.2%), whereas no matching registry entries were found for 38 (35.8%). Inconsistencies were identified in study design, study results, and funding sources, including specific interventions in 8 (11.8%), primary outcome measure (POM) designs in 32 (47.1%), and POM results in 48 (70.6%). In addition, numerous data pieces were unreported, including analysis methods in 52 (76.5%) and POM results in 38 (55.9%)., Conclusions and Relevance: Clinical trial registries were underused in this sample of ophthalmology clinical trials. For studies with registry data, inconsistency rates between published and registered data were similar to those previously reported for general medical literature. In most cases, inconsistencies involved missing data, but explicit discrepancies in methods and/or data were also found. Transparency and credibility of published trials may be improved by closer attention to their registration and reporting.