Citations

ABSTRACT Objectives We evaluated the impact of teprotumumab therapy ( TT ) introduction on orbital decompression ( OD ) utilization for thyroid eye disease ( TED ) and compared rates of significant exophthalmos reduction ( SER ) and diplopia between TT and OD . Methods Newly diagnosed TED patients treated pre (2015–2020) and post teprotumumab (2020–2025) FDA approval were identified from the EHR . Utilization trends, diplopia rates, and immediate (≤ 6 weeks post‐intervention) and long‐term follow‐up SER (≥ 2 mm reduction) were studied. Results Of 406 TED patients, 53 (36.8%) underwent OD in the pre‐ TT cohort ( n = 144). Post‐teprotumumab approval ( n = 262), primary OD was performed in 29 (11.1%), of which 3 (10.3%) were subsequently placed on TT ; primary TT was used in 68/262 (25.9%) with subsequent OD performed in 9 (13.2%). The remaining patients used other treatments (corticosteroids, orbital radiation, rituximab, tocilizumab, etc.). In the overall cohort, immediate SER was achieved in 94.4% of OD versus 83.8% of TT patients ( p = 0.028), with greater median reduction in the OD group (5 vs. 4 mm; p = 0.001). At long‐term follow‐up (median 13 vs. 12 months), SER was sustained in 85.4% of OD and 62.9% of TT patients ( p = 0.042). Pre‐therapy diplopia was more prevalent in TT vs. OD patients (79.4% vs. 59.7%; p = 0.019). New‐onset posttreatment diplopia was higher in the OD group (20.7% vs. 5.9%; p = 0.008). Conclusions Rates of OD surgery declined following FDA approval of teprotumumab. OD achieved sustained and greater exophthalmos reduction but carried a higher risk of diplopia. Contemporaneous OD indications may have evolved to use in TT‐recalcitrant TED or those in need of urgent decompression. Level of Evidence 4.

ABSTRACT Introduction Cytomegalovirus (CMV) causes substantial morbidity after solid organ transplantation. Valganciclovir (VGCV) remains a first‐line prophylactic agent, but it has significant myelosuppressive effect. Letermovir is approved for CMV prophylaxis in high‐risk kidney transplant recipients, but data on its use outside of that population are limited. We describe characteristics and outcomes of letermovir prophylaxis in non‐kidney transplant recipients. Methods We performed a retrospective, multi‐center study of all adult non‐kidney solid organ transplant recipients (SOTr) who received letermovir (March 2018–June 2024) for CMV prophylaxis. Outcomes included breakthrough and post‐prophylaxis delayed‐onset CMV infections, adverse events, and survival. Results A total of 64 patients were included in the final analysis. Of those, letermovir was used for primary prophylaxis in 56.2% of patients, while the remainder received it for secondary prophylaxis. The main rationale behind selecting letermovir was myelosuppression related to VGCV. During the median follow‐up of 361 days (IQR, 190–536), 40.6% remained on letermovir (median, 387 days); 25.0% completed prophylaxis (median, 116 days); and 34.3% discontinued prematurely (median, 49 days), mainly for cost barriers or adverse effects. Breakthrough infections occurred in 9 patients (14.1%), but only three (4.7%) were clinically significant. After stopping letermovir, 39.5% (15/38 among those who discontinued letermovir) developed post‐prophylaxis delayed‐onset CMV infection. Overall survival was 81.2%; there was one death attributed to CMV. Conclusion In this cohort of non‐kidney solid organ recipients, letermovir was well tolerated with low rates of clinically significant breakthrough infections. Early discontinuation was commonly cost‐driven. Post‐prophylaxis delayed‐onset CMV infections remain common. Large‐scale registry studies are needed to provide evidence for use of letermovir in non‐kidney transplant recipients.

Objective Immune checkpoint inhibitor (ICI) myositis is a rare but a highly morbid condition, particularly with the ICI myositis triad syndrome of myositis, myocarditis, and myasthenia gravis. We report the clinical characteristics of ICI myositis and all‐cause mortality in these patients. Methods We performed a national retrospective cohort study of US veterans treated with an ICI between June 2011 and February 2022. Cases were identified by elevated creatinine kinase (CK) following ICI therapy and/or “myositis” in notes. Chart review determined if candidates had ICI‐associated myositis and were subsequently classified as isolated ICI myositis or ICI triad syndrome. Results Of 29,296 veterans treated with ICIs, 68 (0.2%) ICI‐induced myositis cases were identified, including 23 patients with ICI triad syndrome and 45 patients with isolated ICI myositis. Median survival duration for ICI triad syndrome was 2.5 (95% confidence interval [CI] 1.7–18.5) months in comparison to 20.4 (95% CI 6.2–60) months for isolated ICI myositis and 12.6 (95% CI 12.3–12.8) months median survival for patients treated with ICI without myositis. Patients with ICI triad syndrome had 60.0% mortality during the six months following initiation of ICI treatment, in comparison to 30.2% mortality in isolated ICI myositis and 31.5% mortality in patients without myositis. Six months after the first ICI treatment, subsequent mortality trends were similar in the three groups. Conclusion ICI triad syndrome is associated with higher overall mortality and shortened median survival times during the first six months after initial ICI therapy, whereas isolated ICI myositis is associated with similar mortality outcomes compared to patients treated with ICI who did not develop myositis. image

Purpose: Familial history of aortic disease has been associated with increased risk of aneurysm-related complications after standard endovascular aortic repair. The aim of this study was to evaluate outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) for complex aortic aneurysms in patients with or without familial aortic aneurysms (FAAs). Materials and Methods: We reviewed the clinical data of consecutive patients enrolled in a prospective non-randomized study to investigate outcomes after FB-EVAR for treatment of complex aortic aneurysms between 2013 and 2022. Familial aortic aneurysm was defined as occurrence of an aortic aneurysm or dissections in a first- or second-degree relative and compared with patients with sporadic aortic aneurysms (SAAs). Endpoints included procedural metrics, 30-day mortality and major adverse events (MAEs), mid-term patient survival, freedom from reintervention and endoleak, and aneurysm sac shrinkage. Results: There were 499 patients treated with FB-EVAR (70% males, mean age was 74±7.7 years) including 66 (13%) patients with FAAs and 434 (87%) with SAAs. Both groups had similar demographics, clinical characteristics, aneurysm extent, and prior history of aortic dissection or aortic repair. Patients with FAAs had longer fluoroscopy time (82 vs 71 minutes) and radiation exposure (1856 vs 1213 mGy; each p<0.05), with no difference in technical success (FAA, 94% vs SAA, 97%; p=0.51). There was no difference in 30-day mortality (1.5% vs 0.9%; p=1.00) and MAEs (23% vs 18%; p=0.44) among patients with FAA and SAA, respectively. Median follow-up was 28 months. At 3 years, patient survival, freedom from secondary interventions, and cumulative incidence of sac shrinkage were 76±2.5%, 74±2.5%, and 32±2.6% for all patients, respectively, with no difference between FAA and SAA groups. Conclusion: Fenestrated-branched endovascular aortic repair was performed with high technical success, low mortality, and low incidence of MAEs regardless of the presence of FAA. There was no difference in mid-term patient survival, secondary interventions, and sac changes among patients with or without family history of aortic disease. Clinical Impact This study demonstrates that fenestrated-branched endovascular aortic repair (FB-EVAR) can be performed with high technical success and comparable early and mid-term outcomes in patients with or without a familial history of aortic aneurysm, after exclusion of genetically triggered aortic diseases. These findings challenge the assumption that family history alone should preclude complex endovascular repair. Clinically, this supports broader use of FB-EVAR in carefully selected patients with familial aortic disease, emphasizing anatomical suitability rather than pedigree alone. The innovation lies in validating FB-EVAR as a safe alternative to open repair for this understudied population, informing patient selection, counseling, and surveillance strategies.

Abstract INTRODUCTION Understanding comorbidities’ combined impacts on dementia risk may offer a more comprehensive understanding of individuals’ risk. Using machine‐learning, we grouped individuals with similar midlife risk profiles into clusters and explored associations with dementia risk. METHODS Participants without dementia at baseline (1987–1989) from the prospective Atherosclerosis Risk in Communities (ARIC) study were included (ages 45–64 years; N = 15,250). Using unsupervised hierarchical cluster analysis, nine clusters were created and defined based on 14 midlife morbidities. The associations with incident dementia ( N = 3272 cases, median follow‐up 25 years) and deaths ( N = 9099) were evaluated using time‐to‐event regression models. RESULTS Compared with the healthiest cluster (Cluster 1), Clusters 2 (smoking) (hazard ratio [HR](95% confidence interval [CI]) = 1.62 (1.08, 2.43)), 5 (obesity, diabetes, hypertension, and hypertriglyceridemia) (HR(95%CI) = 1.91 (1.35,2.70)), and 7/8 (atrial fibrillation/heart failure) (HR(95%CI) = 2.69 (1.59,4.57)) were associated with dementia. Accounting for competing risk of death in the Fine‐Gray subdistribution model negated the cluster‐dementia association. DISCUSSION Midlife morbidity clusters are important for dementia and mortality risk.

Abstract Sinonasal squamous cell carcinoma (SNSCC) is an aggressive head and neck cancer of the sinonasal cavity which has not benefitted from therapeutic advances over decades 1 . Though historically attributed to inhaled carcinogens such as hardwood dust and tobacco smoking 2 , SNSCC is incidentally associated with human papillomavirus (HPV) 3,4 . Importantly, HPV is the primary oncogenic driver of >80% of anatomically adjacent oropharyngeal cancers 5 . While viral status drives clinical staging and treatment guidelines in these malignancies 6,7 , the potentially oncogenic consequences and prognostic value of host–virus interactions in SNSCC remain incompletely defined. Here, through paired host and viral whole-genome sequencing (WGS), we map the genomic footprint of HPV in SNSCC. Strikingly, lesser studied strains such as HPV45, 51, and 39 constitute driver infections in this rare but clinically credentialed cancer, where extrachromosomal DNA (ecDNA)-associated viral integration and APOBEC mutagenesis are shown to underpin somatic tumor evolution. Statement of Significance Paired host viral and whole-genome sequencing of SNSCC nominates HPV as a primary oncogenic driver of SNSCC. HPV–human ecDNA amplicons harboring noncanonical strains such as HPV45, 51 mediate viral carcinogenesis. Routine clinical diagnostic HPV panels should be expanded to capture the activity of lesser studied strains.

Abstract Recurrence scores based on a 21-gene assay are clinically useful for predicting prognosis and chemotherapy benefit in postmenopausal node-positive breast cancer patients, but its performance in premenopausal patients is inconsistent. Here, we evaluated Ataraxis Breast RISK (ATX), an AI test that predicts recurrence risk, and compared it with the genomic assay. ATX identified high risk patients misclassified as low risk by the genomic assay and therefore may refine selection of patients for adjuvant chemotherapy.

Abstract Background The self-management of type 2 diabetes (T2D) typically requires enacting various lifestyle changes, which can challenge people living with T2D. Clinical encounters between people with T2D and their clinicians, however, are often focused on metabolic management, leaving less time available for other self-management topics. The QBSAFE cards help patients articulate aspects of their experience with diabetes and prioritize issues for discussion. Methods This report details secondary outcomes of a randomized controlled trial; primary outcomes are reported elsewhere. All data was collected at Fair Haven Community Health Care, a federally qualified primary care clinic. 11 clinicians were randomly assigned to provide either usual care or usual care with QBSAFE cards to 155 of their patients with type 2 diabetes and hemoglobin A1c >8%. All patient encounters were video recorded for analysis. Patients and clinicians were not blinded to arm allocation but were kept unaware of the specific aims of the trial. Encounter video reviewers were blinded to arm allocation, but not to specific aims of the trial. The outcomes of interest for this report were the extent to which the QBSAFE cards were used as intended, their effect on the topics of discussion, and whether they enabled clinicians to notice and respond to each patient’s situation; comparisons between arms were conducted by a linear mixed model with fixed effect of arm and cluster effect of clinician, analyzed in both intent-to-treat and per-protocol populations. Findings 12 patients were excluded post-randomization (A1c <8%). Of 143 eligible patients, 137 encounters (65 in the usual care arm, 72 in QBSAFE) yielded evaluable videos. QBSAFE was used as intended in 61 (85%) QBSAFE arm encounters. Conversations about burden of treatment related to non-pharmacological interventions (17 vs 33, p = 0·04) and taking medications (11 vs 33, p = 0·0008) and about the patient’s challenging environment (2 vs 10, p = 0·04) were more prevalent in the QBSAFE group. There was no difference in the rate of conversations about metabolic management or of new care plans as a result of conversations between groups. Interpretation While there was a difference in the types of conversations observed between the two study arms, this difference was small and only apparent in a few domains. Future work could aim to modify the QBSAFE cards to more effectively stimulate patient-centered discussions and to further prepare clinicians to respond to a variety of issues raised during the clinical visit. Funding This work was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK129616).