Citations

Abstract Aims The Shock Academic Research Consortium (SHARC) recently proposed pragmatic consensus definitions to standardize classification of cardiogenic shock (CS) in registries and clinical trials. We aimed to describe contemporary CS epidemiology using the SHARC definitions in a cardiac intensive care unit (CICU) population. Methods and results The Critical Care Cardiology Trials Network (CCCTN) is a multinational research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Cardiogenic shock was defined as a cardiac disorder resulting in SBP < 90 mmHg for ≥30 min [or the need for vasopressors, inotropes, or mechanical circulatory support (MCS) to maintain SBP ≥ 90 mmHg] with evidence of hypoperfusion. Primary aetiologic categories included acute myocardial infarction-related CS (AMI-CS), heart failure-related CS (HF-CS), and non-myocardial (secondary) CS. Post-cardiotomy CS was not included. Heart failure-related CS was further subcategorized as de novo vs. acute-on-chronic HF-CS. Patients with both cardiogenic and non-cardiogenic components of shock were classified separately as mixed CS. Of 8974 patients meeting shock criteria (2017–23), 65% had isolated CS and 17% had mixed shock. Among patients with CS (n = 5869), 27% had AMI-CS (65% STEMI), 59% HF-CS (72% acute-on-chronic, 28% de novo), and 14% secondary CS. Patients with AMI-CS and de novo HF-CS were most likely to have had concomitant cardiac arrest (P < 0.001). Patients with AMI-CS and mixed CS were most likely to present in more severe shock stages (SCAI D or E; P < 0.001). Temporary MCS use was highest in AMI-CS (59%). In-hospital mortality was highest in mixed CS (48%), followed by AMI-CS (41%), similar in de novo HF-CS (31%) and secondary CS (31%), and lowest in acute-on-chronic HF-CS (25%; P < 0.001). Conclusion SHARC consensus definitions for CS classification can be pragmatically applied in contemporary registries and reveal discrete subpopulations of CS with distinct phenotypes and outcomes that may be relevant to clinical practice and future research.

Abstract Although the 2022 European LeukemiaNet (ELN) acute myeloid leukemia (AML) risk classification reliably predicts outcomes in younger patients treated with intensive chemotherapy, it is unclear whether it applies to adults ≥60 years treated with lower-intensity treatment (LIT). We aimed to test the prognostic impact of ELN risk in patients with newly diagnosed (ND) AML aged ≥60 years given LIT and to further refine risk stratification for these patients. A total of 595 patients were included: 11% had favorable-, 11% intermediate-, and 78% had adverse-risk AML. ELN risk was prognostic for overall survival (OS) (P < .001) but did not stratify favorable- from intermediate-risk (P = .71). Within adverse-risk AML, the impact of additional molecular abnormalities was further evaluated. Multivariable analysis was performed on a training set (n = 316) and identified IDH2 mutation as an independent favorable prognostic factor, and KRAS, MLL2, and TP53 mutations as unfavorable (P < .05). A “mutation score” was calculated for each combination of these mutations, assigning adverse-risk patients to 2 risk groups: −1 to 0 points (“Beat-AML intermediate”) vs 1+ points (“Beat-AML adverse”). In the final refined risk classification, ELN favorable- and intermediate-risk were combined into a newly defined “Beat-AML favorable-risk” group, in addition to mutation scoring within the ELN adverse-risk group. This approach redefines risk for older patients with ND AML and proposes refined Beat-AML risk groups with improved discrimination for OS (2-year OS, 48% vs 33% vs 11%, respectively; P < .001), providing patients and providers additional information for treatment decision-making.

PURPOSE The enhanced, electronic health record (EHR)–facilitated cancer symptom control (E2C2) trial is a cohort cluster-randomized, stepped-wedge, hybrid type II trial that leverages EHR systems to facilitate a collaborative care model (CCM) approach with the goal of improving cancer symptom management. Understanding factors that influence care team adoption of EHR systems remains a critical understudied area of research. This study examines how oncology care teams' perceptions regarding the feasibility, acceptability, and appropriateness of E2C2 EHR systems preimplementation were associated with adoption 3 months after implementation and characterizes differences in adoption by individual- and system-level factors. METHODS Care team members completed an electronic survey before and 3 months after implementation of E2C2 for their respective sequence. Adoption was defined as frequency of use to statements aligned with care team–directed EHR systems designed to facilitate CCM approaches. Chi-square tests assessed differences in adoption while logistic regression models estimated associations between baseline mean scores of acceptability, feasibility, and appropriateness on care team adoption at 3 months. RESULTS Results from 94 care team members (37.2% oncologists, 72.6% female, 55.3% in their role for 6+ years) found that adoption rates ranged from 48.9% to 71.7%, with significant differences observed by location (community-based health care systems v tertiary medical center) and professional role. Adjusting for professional role, care team members reporting higher levels of perceived acceptability and appropriateness at baseline had greater odds of adopting EHR systems at 3 months. CONCLUSION EHR systems perceived as acceptable and appropriate are more likely to be adopted by oncology care teams in our sample. Future implementation efforts should consider tailored strategies to facilitate adoption of EHR systems designed to promote CCM-based approaches to improve cancer symptom management.

Abstract The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

Abstract Objectives Urine drug testing (UDT) is a critical tool used in medical, forensic, and occupational settings, but interpreting results can be challenging. We performed a study to assess the ability of health care professionals to interpret UDT results accurately. Methods In total, 911 clinical and laboratory professionals in the United States and Canada responded to a survey with questions gauging expertise in UDT interpretation. Responses were analyzed to identify knowledge gaps. Results Toxicologists and laboratory PhD scientists performed well, with means of 4.82 and 4.63 questions answered correctly (out of 6 possible), respectively. Physicians specializing in pathology, emergency medicine, primary care, and internal medicine, however, displayed concerning knowledge gaps, as did laboratorians with nondoctoral degrees. Experience and training correlated with interpretation accuracy. Identification of simulated compliance as well as understanding opioid exposure, metabolism, and immunoassay cross-reactivity were among the most clinically significant knowledge gaps. More than 30% of survey respondents indicated that they would seek UDT information from the internet or peers rather than clinical or laboratory experts. Conclusions The study highlighted the need for targeted education and better collaboration between clinical and laboratory experts and other health care professionals to ensure that when physicians order UDT, they can accurately interpret results and reduce harm.

ImportanceCutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited.ObjectiveTo define standardized reporting measures for retrospective CSCC studies.FindingsAn expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses.Conclusions and RelevanceThe recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

OBJECTIVE To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference −12 mg/dL, 95% CI −22 to −2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group. CONCLUSIONS Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.

Abstract Purpose Rapid sequence intubation (RSI) is a common emergency department (ED) procedure with an associated complication of postintubation hypotension (PIH). It has not been clearly established whether the selection and dose of induction agent affect risk of PIH. The objective of this study was to determine the incidence of PIH in patients receiving full-dose compared to reduced-dose induction agent for RSI in the ED. Methods This was a health system–wide, retrospective cohort study comparing incidence of PIH based on the induction medication and dose given for RSI in the ED. Patients were included if they underwent RSI from July 1, 2018, through December 31, 2020, were 18 years of age or older, and received etomidate or ketamine. A reduced dose was defined as a ketamine dose of 1.25 mg/kg or less and an etomidate dose of 0.2 mg/kg or less. Results A total of 909 patients were included in the final analysis, with most receiving etomidate (n = 764; 84%) and a smaller number receiving ketamine (n = 145; 16%). Patients who received ketamine had a higher mean pre-intubation shock index (full dose, 1.08; reduced dose, 1.04) than those who received etomidate (full dose, 0.89; reduced dose, 0.92) (P ≤ 0.001). Reduced doses of induction agent were observed for 107 patients receiving etomidate (14.0%) and 60 patients receiving ketamine (41.4%). Patients who received full-dose ketamine for induction had the highest rate of PIH (n = 31; 36.5%), and the difference was statistically significant compared to patients receiving reduced-dose ketamine (16.7%; P = 0.021) and full-dose etomidate (22.8%; P = 0.010). Conclusion We observed that full-dose ketamine was associated with the highest rate of PIH; however, this group had the poorest baseline hemodynamics, confounding interpretation. Our results do not support broad use of a reduced-dose induction agent.

Abstract The scaphotrapeziotrapezoid (STT) joint is involved in load transmission between the wrist and thumb. A quantitative description of baseline STT joint morphometrics is needed to capture the variation of normal anatomy as well as to guide staging of osteoarthritis. Statistical shape modeling (SSM) techniques quantify variations in three‐dimensional shapes and relative positions. The objectives of this study are to describe the morphology of the STT joint using a multi‐domain SSM. We asked: (1) What are the dominant modes of variation that impact bone and articulation morphology at the STT joint, and (2) what are the morphometrics of SSM‐generated STT joints? Thirty adult participants were recruited to a computed tomography study of normal wrist imaging and biomechanics. Segmentations of the carpus were converted to three‐dimensional triangular surface meshes. A multi‐domain, particle‐based entropy system SSM was used to quantify variation in carpal bone shape and position as well as articulation morphology. Articular surface areas and interosseous proximity distributions were calculated between mesh vertex pairs on adjacent bones within distance (2.0 mm) and surface‐normal angular (35°) thresholds. In the SSM, the first five modes of variation captured 76.2% of shape variation and contributed to factors such as bone scale, articular geometries, and carpal tilt. Median interosseous proximities—a proxy for joint space—were 1.39 mm (scaphotrapezium), 1.42 mm (scaphotrapezoid), and 0.61 mm (trapeziotrapezoid). This study quantifies morphological and articular variations at the STT joint, presenting a range of normative anatomy. The range of estimated interosseous proximities may guide interpretation of imaging‐derived STT joint space.