Citations

Background. Measles, mumps, and rubella (MMR) in solid organ transplant (SOT) recipients is rare. We aim to investigate the pretransplant seroprevalence, MMR infection posttransplant, and whether immediate pretransplant MMR vaccination is associated with MMR infection. Methods. We queried the TriNetX database in December 2024 to assess (1) pretransplant MMR seroprevalence, (2) characteristics and outcomes of posttransplant MMR infections, and (3) outcomes for recipients who received the MMR vaccine within 30 d pretransplant. Only US data were included. MMR infection was identified through International Classification of Diseases (ICD) codes. Results. Among 313 548 SOT recipients identified in the database (from 2009 to 2024), IgG positivity for MMR was 72%, 80%, and 78% when available (~5% each). Based on ICD codes, posttransplant MMR infections occurred in 107 (0.03%), 124 (0.04%), and 38 (0.01%) recipients, respectively. The 90-d rejection rates were 36%, 27%, and 42%, whereas mortality rates were 7%, 8%, and 5%, respectively, in patients with MMR infection. Among 114 recipients vaccinated within 30 d pretransplant, none developed posttransplant MMR infections. Conclusions. Overall, posttransplant MMR infections in adult SOT recipients were uncommon in this data set, and no vaccine-associated infections were documented among those who received the MMR vaccine within 30 d pretransplant in real-world practice. The primary limitation of this study is that most MMR infections were identified using ICD codes without confirmation through serological testing or polymerase chain reaction, and we were unable to further characterize the infections because the de-identified database lacked information on the patient’s ZIP code and transplant hospital. Our study highlights the need for improvement in MMR serology screening and pretransplant MMR vaccination.

PURPOSE Lack of race- and age-diversity in clinical trials adversely affects generalizability of trial results and equity of trial access. Research on barriers to representative accrual has focused on patient-level factors. We aimed to define site-level factors affecting the diversity of accrual to a multicenter clinical trial. METHODS Alliance 191901 (GETSET) is a national randomized controlled trial testing interventions to promote breast cancer endocrine therapy adherence, which oversamples Black women and those under age 50 years at 30% thresholds. A secondary study objective is to examine site-level factors associated with accrual of Black and younger participants. At 50% accrual to the parent study, we performed prespecified analyses of association between site characteristics (region, neighborhood racial composition, Alliance membership type, number of recent accruals to cooperative research group trials) and the proportion of Black patients and younger patients accrued. We also examined trajectories of accrual over time for race- and age-specified subgroups. RESULTS The analysis included 124 sites. Among 590 participants, 9.7% were Black, and 22.4% were age <50 years. Neither site type nor historical accrual volume was associated with Black participant recruitment. Southern sites recruited higher proportions of Black participants (19.0% v 7.3% for West, P < .001). Neighborhood racial composition was positively associated with recruitment of Black participants (16.2% at sites from highest Black composition v 1.4% in lowest, P < .01). Recruitment trajectories of Black participants were slower than target rates, whereas those among non-Black participants were faster. CONCLUSION Neighborhood composition and geographic region were predictors of proportions of Black participants accrued to A191901 sites, but site type and historical accrual volume were not. When trials must limit site selection, identifying sites based on neighborhood composition and geography may be an appropriate tool for increasing trial diversity.

Background: Patients with non-English Language Preference are at risk of adverse health outcomes, particularly at end of life and during serious illness. Medical interpreters often feel unprepared to interpret conversations about serious illness. Best practice guidelines recommend a pre-encounter huddle between clinician and interpreter to better prepare both providers. The CHECK-IN (Check in for Exchange of Clinical and Key Information) guide is a simple communication tool designed to facilitate this pre-encounter huddle. We describe the results of a pilot feasibility study of the CHECK-IN guide performed in a simulation environment. The primary objectives of the study were to evaluate the feasibility, acceptability, and preliminary performance of the CHECK-IN guide. Methods: This U.S.-based study is a single-center simulation-based nonblinded randomized pilot feasibility study. Participating clinicians were randomized to usual practice (control) vs. introduction to the CHECK-IN guide (intervention). Clinicians completed pre- and post-session surveys. Participating clinicians were evaluated using the Faculty Observation Rating Scale (FORS), Interpreter Scale (IS), and Interpreter Impact Rating Scale (IIRS). Results: Participants had a highly favorable opinion on the acceptability, appropriateness, and feasibility of the CHECK-IN tool; 91% of participants agreed/strongly agreed on the acceptability of the tool, 91% agreed/strongly agreed on the appropriateness of the tool, and 100% agreed/strongly agreed on the feasibility of the tool. There were no statistical differences between control and intervention groups for the IS, IIRS, and FORS scores. Conclusion: The CHECK-IN guide is a promising tool to guide a pre-encounter huddle between clinician and interpreter, thereby improving interpreter-mediated communication when having conversations about serious illness.

Anthracyclines are potent chemotherapeutic agents, yet their clinical use is hampered by their cardiotoxicity. Anthracyclines achieve potent anti- cancer effects primarily via TOP2A, but at the same time they induce a dose limiting cardiotoxicity through TOP2B. The use of a catalytic TOP2 inhibitors such as dexrazoxane (ICRF 187) significantly reduces the incidence of anthracycline-induced cardiotoxicity. However, dexrazoxane targets the highly conserved TOP2 dimer interface that is identical between TOP2A and TOP2B, fostering persisting concerns that its inhibition of TOP2A isoenzyme may interfere with anthracycline anticancer effects and augment anthracycline-induced myelosuppression. Thus, isoform- selective TOP2 inhibitors that can control the DNA damage caused by TOP2A vs TOP2B are a significant unmet clinical need. We have developed a new class of highly potent and TOP2B-selective catalytic inhibitors through rational design by building upon the general pharmacophore present in isolates from Calophyllum Brasiliense. Using X-ray crystallography, we demonstrate that our newly developed compounds occupy a previously unidentified druggable binding-site in the TOP2 ATPase domain and function as a physical barrier to block the conformational change triggered by ATP hydrolysis. We have named the class of inhibitors that target this site “obex”, the Latin word for obstacle. The obex binding site contains residues that differ between the TOP2A and TOP2B isoenzymes, based on which we rationally designed, prepared, and systematically evaluated a targeted panel of obex inhibitors. We have identified the lead molecule, namely, topobexin, as the first- in-class TOP2B-specific obex inhibitor that can prevent anthracycline-induced DNA damage. This first TOP2 isoform-specific inhibition underscores the broader potential to improve drug specificity and minimize adverse effects in various medical treatments.

This case report discusses a patient with vertebral pseudoaneurysm that spontaneously ruptured and led to vertebro-vertebral arteriovenous fistula requiring endovascular therapy.

Importance Adverse events in otolaryngology–head and neck surgery (OHNS) are inconsistently reported. The Clavien-Dindo Classification has been modified and validated in several surgical subspecialties but has yet to be validated in OHNS. Objective To create and validate a modified Clavien-Dindo Classification for OHNS that reflects the severity and duration of harm for complications experienced by patients undergoing OHNS. Design, Setting, and Participants This is a multicenter survey study of subject matter experts (SMEs) from OHNS subspecialties from academic institutions within the US. A literature review identified publications reporting surgical complications in OHNS in the English language between January 2019 and April 2020. Complications were summarized and used to inform a modified Clavien-Dindo Classification. Feedback from internal SMEs was incorporated. Thirty-five clinical vignettes were created, and an electronic survey was sent to SMEs at outside institutions. Each SME was randomly assigned to 1 of 4 groups to evaluate 8 to 9 vignettes. The survey was conducted in September 2023, and data were analyzed from February to May 2024. Exposure Participation in the electronic survey. Main Outcomes and Measures Vignette scores were assessed and the Comprehensive Complication Index (CCI) calculator was used to assess cumulative morbidity. The scale is based on the grading by the Clavien-Dindo Classification and reflects overall morbidity on a scale from 0 (no complication) to 100 (death). Variability of the CCIs between reviewers, the primary outcome, was summarized with the SD. The percentage of reviewers with a high (≥26.2) or low (&amp;lt;26.2) CCI within a vignette was reported. Reliability was summarized using Krippendorff α. Results Of 106 SMEs, 43 (response rate, 40.6%) completed at least 1 vignette. Eighteen of 35 vignettes (51.4%; 95% CI, 34.9%-68.0%) had unanimous high CCI, and 8 of 35 vignettes (22.9%; 95% CI, 8.9%-36.8%) had unanimous low CCI (overall categorical agreement, 74.3%; 95% CI, 59.8%-88.8%). On average, the Krippendorff α was 0.74, indicating moderate reliability. A total of 21 850 OHNS complications were reviewed and categorized as surgical or medical with 12 including subcategorization for specificity. Each category was then assigned a modified OHNS Clavien Dindo classification grade. Conclusions and Relevance In this survey study of OHNS experts, a modified OHNS Clavien-Dindo Classification was developed and validated using case vignettes. The modified Clavien-Dindo Classification provided a granular subcategorization for each complication category and grade, duration of harm, and an overall summary complication score (CCI). Results suggest the modified OHNS Clavien-Dindo Classification reliably differentiated between high-grade and low-grade OHNS complications and could be utilized for assessing surgical outcomes.

Abstract Purpose: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used. Experimental Design: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL. Results: Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77–3.84; P &lt; 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66–4.02; P &lt; 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5–0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP. Conclusions: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.

ABSTRACT We report the first known use of a trans-sigmoidal endoscopic ultrasound-guided biopsy in a patient with a simultaneous pancreas-kidney transplant, following failed conventional percutaneous biopsy methods. A 50-year-old man with a simultaneous pancreas-kidney transplant was suspected of graft dysfunction. Multiple percutaneous biopsies were unsuccessful due to anatomical barriers. After a multidisciplinary review, a trans-sigmoidal endoscopic ultrasound approach was attempted, yielding sufficient tissue for histopathology without complications. Histology revealed no evidence of acute rejection. This novel technique expands the potential for biopsy in complex transplant anatomies and should be considered in highly selected cases within specialized centers.