Faculty Bibliography

BACKGROUND/UNASSIGNED:Effective management of alcohol withdrawal syndrome during hospitalization is paramount to patient safety and quality care. NYC Health + Hospitals initiated a quality improvement project to pilot an electronic health record (EHR) integrated, nurse-driven CIWA-Ar symptom-triggered protocol, including recommendations for medications for alcohol use disorder (MAUD), in medical and surgical units at 3 public hospitals. OBJECTIVE/UNASSIGNED:To describe implementation processes and to report related implementation outcomes (appropriateness, feasibility, and adoption) of the updated CIWA-Ar protocol in a safety net hospital setting. METHODS/UNASSIGNED:NYC Health + Hospitals implemented a standardized CIWA-Ar symptom-triggered, nurse-driven EHR protocol on March 15, 2022. The protocol included order sets, practice advisories, task lists, and reminders for assessments and orders. We measured nursing perspectives on feasibility and appropriateness at 6 months via a survey. We measured provider adoption as the proportion of admissions with a CIWA-Ar protocol ordered among admissions that triggered a recommendation, and MAUD use as the proportion of admissions with a MAUD order during hospitalization among all patients with a protocol ordered. RESULTS/UNASSIGNED:= .249). CONCLUSIONS/UNASSIGNED:The CIWA-Ar protocol was appropriate, feasible, and adopted at NYC public hospitals. Quality improvements to ensure protocol fidelity with benzodiazepine dosing and MAUD prescribing are needed.

PURPOSE/OBJECTIVE:Pancreatic cystic lesions (PCL) commonly undergo surveillance using MRI with MR cholangiopancreatography (MRCP). Our objective is to compare the performance of a single-shot fat-saturated T2-weighted technique with deep-learning reconstruction (DL HASTE-FS) to a conventional T2-weighted Half fourier Single-shot Turbo spin-Echo (HASTE) sequence and to MRCP for the purpose of PCL detection, characterization, and surveillance. METHODS:In this retrospective study, 91 consecutive patients underwent 3T abdominal MRI with MRCP protocol including DL HASTE-FS and conventional HASTE between 8/2/2023 and 10/3/2023. Three abdominal radiologists rated overall and lesion-specific image quality on a 5-point Likert scale, including pancreatic margin and duct sharpness, and PCL conspicuity. A subset of 70 preselected index PCLs were evaluated for cyst features, confidence of diagnosing side-branch IPMN, and suitability of DL HASTE-FS in replacing MRCP for PCL surveillance. RESULTS:DL HASTE-FS received higher scores for pancreatic duct border sharpness (4.1 vs. 3.9; p = .004), pancreatic duct visibility compared to MRCP (2.0 vs. 1.9; p = .04), cyst conspicuity (4.4 vs. 3.9; p < .001), and sharpness of cyst wall and internal septations (4.3 vs. 3.7; p < .001) compared to conventional HASTE. In contrast, conventional HASTE received higher scores for pancreatic margin sharpness (4.2 vs. 3.8; p < .001) and peripancreatic vessel clarity (4.2 vs. 3.4; p < .001). For the 70 preselected index PCLs, readers visualized more PCLs and had higher confidence in diagnosing SB-IPMN on DL HASTE-FS than on conventional HASTE (3.6 vs. 3.4; p < .001). Finally, DL HASTE-FS was deemed a suitable replacement to MRCP for more cases than conventional HASTE (83% vs. 48%; p < .001). CONCLUSION/CONCLUSIONS:DL HASTE-FS outperforms conventional HASTE for PCL detection and characterization, and is a suitable alternative to 3D MRCP in the context of PCL surveillance, potentially reducing exam time and cost.

BACKGROUND:Coronary microvascular dysfunction (CMD) is present in approximately 40% of patients with ischemia with no obstructive coronary arteries (INOCA) and has been associated with inflammation. We investigated associations between measures of inflammation of the coronary perivascular adipose tissue assessed by coronary computed tomography angiography (CCTA) and results of invasive coronary function testing (CFT) to diagnose CMD. METHODS:Adults referred for clinically indicated invasive coronary angiography who had less than 50% stenosis in all epicardial arteries were prospectively enrolled. CMD was defined as a coronary flow reserve (CFR) less than 2.5 or index of microvascular resistance (IMR) greater than or equal to 25 using bolus thermodilution in the left anterior descending (LAD) coronary artery. Coronary perivascular fat attenuation index was assessed by CCTA in the right coronary artery (RCA) and LAD. T tests were used to evaluate differences in perivascular FAI by CMD status. RESULTS:A total of 31 participants underwent CFT and CCTA. The mean age was 58 ± 11.7 years, 77% were female, and 61% were white. CMD was present in 15 participants (48%). No differences in perivascular FAI were observed in patients with and without CMD, either in the RCA [-74.2 ± 9.8 vs. -69.9 ± 10.3 Hounsfield units (HU), P = 0.24] or LAD (-76.4 ± 10.2 vs. -74.8 ± 12.7 HU, P = 0.69). Perivascular FAI was not correlated with CFR or IMR measurements in the RCA or LAD. CONCLUSION/CONCLUSIONS:There were no associations between CMD diagnosed by invasive CFT and perivascular FAI by CCTA in patients with INOCA. Further research is needed to understand the relationship between vascular inflammation and CMD in INOCA.

Lung cancer remains the leading cause of cancer-related deaths worldwide, partly because many patients are diagnosed at late stages, highlighting the urgent need for effective early detection and intervention strategies. Low-dose computed tomography (LDCT)-based screening reduces lung cancer mortality in high-risk populations defined by age and smoking history; however, the uptake of LDCT remains low among eligible individuals. Compounding this issue, modelling studies estimate that nearly half of lung cancers occur in individuals who do not meet eligibility criteria for LDCT-based lung cancer screening under current guidelines. Moreover, LDCT-based screening has inherent limitations, including a high rate of false-positive results that can lead to unnecessary invasive procedures, as well as substantial costs that limit scalability. Major efforts have been made to identify novel biomarkers such as radiomic features and liquid biopsy assays to enhance the accuracy of lung cancer risk prediction. Furthermore, the increasing detection of pulmonary nodules by LDCT or diagnostic CT scans has highlighted the importance of therapeutic interventions that can enable interception of high-risk precancerous nodules and halt their progression to invasive disease. In this Review, we summarize the current state of lung cancer screening, the disparities and infrastructural considerations for optimal implementation, and future directions in the development of biomarkers and design of precancer interception strategies that could transform both lung cancer prevention and early intervention.

BACKGROUND:Due to high prevalence of Kaposi Sarcoma (KS)-Associated Herpesvirus (KSHV) among people with HIV, KSHV-associated disease (KAD) may be increased after kidney transplantation from donors with HIV (HIV D+) to recipients with HIV (HIV R+). METHODS:Anti-KSHV antibodies were measured in HIV R+ and donors with and without HIV (HIV D-) using a 30-antigen multiplex assay within three multicenter kidney transplantation studies. KSHV seropositivity was defined as reactivity to conventional KSHV antigens (≥1 ORF73 or K8.1); reactivity to expanded 5-antigen and 30-antigen panels were also reported. Risk factors were identified using modified Poisson regression. Recipients were monitored for post-transplant anti-KSHV antibody changes and KAD. RESULTS:KSHV seroprevalence was 40.6% (143/352) among HIV R+, 25.2% (33/131) among HIV D+, and 7.5% (4/53) among HIV D-. In the multivariable model, only men who have sex with men (MSM) was associated with KSHV seropositivity: relative risk 1.51 (95% confidence interval [CI] 1.07-2.14) in recipients and 2.39 (95%CI 1.03-5.53) in donors. Among 418 HIV R+ (215 HIV D+/R+, 203 HIV D-/R+), there were 5 KAD cases (incidence 0.63 cases/100 person-years, 95%CI 0.26-1.52): 3 skin-only KS, 1 multicentric Castleman disease, 1 allograft KS. The allograft KS occurred in a female HIV D+/R+ and was likely donor-derived. Remaining KAD cases occurred in male HIV D-/R+ and were likely recipient KSHV reactivation or acquisition. CONCLUSIONS:In the United States, KSHV seroprevalence in donors and recipients with HIV was high, particularly among MSM. Reassuringly, KSHV-associated disease was rare, and primarily attributed to recipient rather than donor-derived KSHV.

The Phase 1/2 Intergroup study E4412 (NCT01896999; ClinicalTrials.gov) investigated checkpoint blockade with nivolumab (Nivo) and ipilimumab (Ipi) in relapsed/refractory (R/R) classic Hodgkin lymphoma (HL) while concurrently targeting CD30+ Hodgkin Reed Sternberg cells with the antibody-drug conjugate brentuximab vedotin (BV). 147 patients ≥12 years were randomized between BV/Nivo and BV/Ipi/Nivo; 132 patients are included in primary efficacy analysis. The primary endpoint, complete response (CR) rate, was 64.7% (52.2, 75.9) for BV/Nivo and 70.3% (57.6, 81.1) for BV/Ipi/Nivo (one-sided p=0.29). The median survival follow-up is 38.0 months (interquartile range 32.6-48.1). Progression-free survival (PFS) did not significantly differ between the two arms (HR=0.78, CI 0.39-1.57, one-sided p=0.24). Treatment-related grade 3+ toxicities in the adult cohort, excluding rash, was similar between both arms (38.5% BV/Nivo and 39.3% BV/Ipi/Nivo); there was higher frequency of grade 3 rash with BV/Ipi/Nivo (24.6%) compared to BV/Nivo (9.2%). We compared PFS by stem cell transplantation (SCT) status in a planned post-hoc comparison; 58 patients received SCT; 36-month PFS (from SCT) was greater than 90% for both arms. Sixty-six patients were alive and progression free after the first scan (disease evaluation) and did not undergo SCT. The 36-month PFS (from first scan) was 73.0% (54.5, 85.0) for BV/Ipi/Nivo compared to 45.8% (26.3, 63.4) for BV/Nivo (HR=0.45, CI 0.19-1.08, one-sided p=0.03). The study did not meet its primary endpoint of superior CR rate for the triplet, but it supports the use of checkpoint-ADC induction prior to auto SCT, and there is an intriguing signal of disease control for patients wishing to defer or avoid SCT for the triplet of BV/Ipi/Nivo.

BACKGROUND:There is emerging literature describing clinical characteristics and outcomes in patients with mpox treated with tecovirimat. METHODS:We analyzed retrospective deidentified data from healthcare systems in New York City with the highest number of tecovirimat prescriptions. Individuals with probable or confirmed mpox initiating tecovirimat from May-December 2022 were included. A chart abstraction instrument was used to extract demographic and clinical data from medical records. We examined factors associated with delay in treatment and hospitalization. RESULTS:A total of 708 individuals prescribed tecovirimat for mpox were included in the analysis; median age was 36 years (IQR 31-43); 566 (80%) were cisgender men who have sex with men; and 399 (56%) were living with HIV. Side effects (100, 14%) and severe adverse events (7, 1%) were rare. The most common long-term sequela was scarring (69, 10%). One hundred and one (14%) were hospitalized. Median time from symptom onset to treatment initiation was 8 days (IQR 6-11). Non-Hispanic Black patients had higher risk of initiating tecovirimat ≥8 days after symptom onset (relative risk [RR]=1.3, 95%CI: 1.2-1.7) and being hospitalized (adjusted relative risk [aRR]=2.2, 95%CI: 1.4-3.5) compared with Hispanic patients, after adjusting for HIV and insurance status. CONCLUSIONS:We described common reasons for tecovirimat initiation and hospitalization. There were racial inequities in hospitalization and treatment delays. More research and focused efforts to mitigate these inequities are needed. These findings may better inform decisions for treatment initiation and hospitalization for mpox.

BACKGROUND:)-mutant non-small-cell lung cancer (NSCLC). Zongertinib is an oral, irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing wild-type epidermal growth factor receptor (EGFR), thereby minimizing associated toxic effects. METHODS:-mutant NSCLC. Here, we evaluated zongertinib at a dose of 120 mg once daily in patients who had not previously received treatment (cohort 2). The primary end point was objective response as assessed by blinded independent central review. Secondary end points included duration of response and progression-free survival. In addition, zongertinib was evaluated in patients with active brain metastases (exploratory cohort 4). RESULTS:In cohort 2, a total of 74 previously untreated patients received zongertinib at a dose of 120 mg. As of August 21, 2025, the percentage of patients with a confirmed objective response was 76% (95% confidence interval [CI], 65 to 84); the median duration of response was 15.2 months (95% CI, 9.8 to not evaluable), and the median progression-free survival was 14.4 months (95% CI, 11.1 to not evaluable). Adverse events of any grade occurred in 73 patients (99%), including events of grade 3 or higher in 33 patients (45%). Treatment-related adverse events occurred in 67 patients (91%), including events of grade 3 or higher in 14 patients (19%). In cohort 4, a total of 30 patients with active brain metastases received zongertinib at a dose of 120 mg; of these, 47% (95% CI, 30 to 64) had a confirmed intracranial objective response according to Response Assessment in Neuro-Oncology Brain Metastases criteria. In this cohort, treatment-related adverse events of grade 3 or higher occurred in 5 patients (17%). CONCLUSIONS:-mutant NSCLC. Treatment-related adverse events were predominantly low-grade. (Funded by Boehringer Ingelheim; Beamion LUNG-1 ClinicalTrials.gov number, NCT04886804.).