Faculty Bibliography

IMPORTANCE/UNASSIGNED:Screening by low-dose computed tomography can reduce lung cancer mortality among high-risk individuals, but many lung cancers occur among individuals with a smoking history who are not eligible for screening. OBJECTIVE/UNASSIGNED:To develop and validate the protein-based Integrative Analysis of Lung Cancer Risk and Etiology (INTEGRAL)-Risk model in individuals with a smoking history from the general population. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Cohorts in the Lung Cancer Cohort Consortium recruited research participants in the US, Europe, Asia, and Australia between 1985 and 2009, who were followed up for lung cancer and other health outcomes until 2021. Fourteen case cohorts of 3695 participants with a smoking history within the Lung Cancer Cohort Consortium, including 2305 randomly sampled participants and 1390 patients diagnosed with lung cancer within 3 years after blood sample collection, were designed. Plasma or serum samples from each participant were assayed using the INTEGRAL protein panel in 2022. The INTEGRAL-Risk model was trained using 7 predefined case cohorts (training set; n = 1951) to estimate absolute risk of being diagnosed with lung cancer based on age, smoking history, and 13 proteins. The validity of the INTEGRAL-Risk model was assessed in 7 independent case cohorts (testing set; n = 1744) at 1, 2, and 3 years after blood collection. EXPOSURE/UNASSIGNED:Absolute risk estimates from the protein-based INTEGRAL-Risk model. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was the validity of the INTEGRAL-Risk model in the testing set with respect to discrimination (area under the curve [AUC]) and calibration (ratio of expected-to-observed cases [E/O]). RESULTS/UNASSIGNED:A total of 3695 participants were included, with 1951 participants (including 807 with lung cancer) in the training set and 1744 participants (including 583 with lung cancer) in the testing set. In the combined 14 training and testing sets, after application of statistical weights, 323 570 participants were represented (185 016 [57%] female; median [IQR] age, 60 [51-67] years). In the independent testing set, discrimination of the INTEGRAL-Risk model was highest at 1 year of follow-up and exceeded that of the questionnaire-based PLCOm2012 (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) model (INTEGRAL-Risk AUC of 0.88 [95% CI, 0.85-0.91] vs PLCOm2012 AUC of 0.79 [95% CI, 0.75-0.83]; P value for difference <.001). Using a risk threshold to achieve the same specificity as US Preventive Services Task Force (USPSTF) 2021 criteria, the INTEGRAL-Risk model captured 85% of lung cancer cases compared with 63% by USPSTF 2021 and 70% by PLCOm2012. Discrimination of the INTEGRAL-Risk model decreased with longer prediction horizons, with a 2-year AUC of 0.84 (95% CI, 0.81-0.86) and 3-year AUC of 0.81 (95% CI, 0.79-0.83). The model was well calibrated (E/O over 3 years, 0.87 [95% CI, 0.69-1.14]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Compared with questionnaire-based approaches, the protein-based INTEGRAL-Risk model improved short-term prediction of lung cancer in people with a smoking history. This model has potential to improve selection of high-risk individuals who are most likely to benefit from lung cancer screening.

Primary graft dysfunction (PGD) is a proinflammatory syndrome occurring within the first days following lung transplantation. It is initiated by ischemia-reperfusion injury and perpetuated by donor and recipient immunologic factors, resulting in alveolar damage and progressive hypoxemic respiratory failure.¹ PGD is a known risk factor for both early allograft failure and chronic lung allograft dysfunction (CLAD).² Incidence of severe PGD remains high at 10-25%, though is variable; risk factors for PGD include center experience, underlying recipient disease type, size matching, donor lung storage conditions, operative time, and post-operative management.² Strategies to prevent PGD or mitigate the long -term consequences after it develops, are sorely needed. However, lack of specificity of the current PGD definition may hamper further progress in the field, especially as it pertains to the development of robust and relevant clinical trials. We propose that future modifications of the PGD definition incorporate more objective surrogates of allograft injury and subsequent diffuse alveolar damage, which may improve our ability to accurately study disease pathogenesis and improve outcomes.

PURPOSE OF THE REPORT/OBJECTIVE:To determine the prevalence, etiology, and clinical significance of incidental focal small bowel FDG uptake in patients undergoing PET/CT for staging of non-small bowel cancers. MATERIAL AND METHODS/METHODS:Retrospective review of consecutive FDG PET/CT examinations obtained for cancer staging with incidental focal small bowel radiotracer uptake was performed. Exclusion criteria included known small bowel pathology or insufficient reference standard. Imaging findings assessed included lesion location, number, CT correlate, SUVmax, and presence of metastases outside the bowel. Clinical data included age, sex, cancer clinical setting, origin, and stage. Focal small bowel FDG uptake etiology (benign vs. metastatic) was determined by composite reference standard (histopathology, clinical, and imaging follow-up). Statistical analyses included Wilcoxon rank-sum test, Pearson's χ2 test, Fisher exact test, and ROC curve analyses. RESULTS:In a review of 147,516 PET/CT examinations, incidental focal small bowel FDG uptake was rare, with a prevalence of 0.1% (88/147,516). Most cases were metastatic, 60.2% (53/88), most commonly spread from lymphoma [32.1% (17/53)] and melanoma [30.2% (16/53)]. Metastatic lesions were evenly distributed throughout the ileum [47.2% (25/53)] and jejunum [39.6% (21/53)]. Metastatic focal small bowel FDG uptake was associated with presence of other sites of distant metastases, higher SUVmax, and presence of a CT correlate (P <0.01). CONCLUSIONS:Incidental focal small bowel FDG uptake is rare. Most small bowel hypermetabolic foci are metastatic and are predominantly encountered with melanoma and lymphoma. Multiple imaging and clinical factors helped differentiate between benign and metastatic focal small bowel FDG uptake.

BACKGROUND:The frequency of residual angina and its impact on health status and death following anatomic complete revascularization in symptomatic patients with chronic coronary disease are unknown. METHODS:Data were analyzed from ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial participants randomized to invasive management with baseline angina (Seattle Angina Questionnaire Angina Frequency score <100), no prior coronary artery bypass graft surgery, and anatomic complete revascularization within 90 days of randomization. The primary outcome was frequency of residual angina after revascularization, defined as a Seattle Angina Questionnaire Angina Frequency score <100 within 6 months of randomization. Secondary outcomes included 6-month health status and medication use and 5-year all-cause and cardiovascular death. RESULTS:=0.006). Five-year all-cause and cardiovascular death did not differ significantly between groups. CONCLUSIONS:Residual angina is common (>40%) following anatomic complete revascularization for chronic coronary disease and is associated with reduced quality of life and greater antianginal medication use but no increase in death. REGISTRATION/BACKGROUND:Unique Identifier: NCT01471522.

Maxillectomy results in disruption of palatal continuity and oral-nasal separation, leading to significant impairment of speech intelligibility and communication that requires effective rehabilitative intervention. Hence, this prospective study assessed the speech quality of 30 patients recovering from maxillectomy who were fitted with prostheses for the obturators at baseline, 3 and six months post- insertion. The scores of intelligibility reported by patients and blinded evaluation ratings of evaluators were statistically significant improvements over time. Scores for the average patient increased by 2.03 + 0.45 at initial assessment to 4.23 + 0.57 after 6 months. Evaluation scores increased from 11.87 ± 0.40 → 3.32 ± 0.48 → 4.10 ± 0.46. Thus, we show that obturators prosthetic therapy leads to significant improvements in speech quality in the first few months of follow-up.

Childhood is a period of peak developmental plasticity, involving drastic changes in the maturation of the neural circuitry underlying fear learning. Disruption and atypical development of fear learning are candidate mechanisms underlying child psychopathology. While there is a lack of understanding behind the maturation of fear learning systems in humans, rodent studies in this area delineate the normative development of fear learning systems early in life, and the effects of early threatening and fearful experiences on this developmental trajectory. Here, we review the rodent literature on developmental fear learning, as well as human studies that show translational convergence in typical development and children exposed to early life threat. We identify several gaps in research, including the role that caregivers play in regulating fear learning at different developmental stages and the intergenerational transmission of learned fear. Finally, we provide recommendations on how to address these gaps in a way that would improve our developmental frameworks of fear learning.

PURPOSE/OBJECTIVE:To develop a novel single-shot radial echo planar imaging (ss-rEPI) technique for rapid, distortion-free brain imaging in functional MRI experiments. METHODS:* mapping and QSM. Visual BOLD fMRI experiments were conducted and evaluated against Cartesian EPI measurements. RESULTS:* measurements. CONCLUSION/CONCLUSIONS:modeling is critical for ss-rEPI performance. Advanced reconstruction techniques and self-calibration methods could further enhance its speed, performance, and applicability across diverse MRI techniques.

PURPOSE/OBJECTIVE:Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. METHODS:We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). RESULTS:Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. Propensity-score-matched analyses revealed no significant difference in thromboembolic complications (11.8% vs. 5.9%, p = 0.056), similar periprocedural adequate occlusion (53.3% vs. 53.8%, p > 0.9), and similar retreatment rates (11.8% (95% CI 7.8-17.6%) vs. 7.1% (95% CI 4.1-12.0%), p = 0.14); however, adequate occlusion at follow-up was lower (82.2% vs. 93.3%, p = 0.002) and functional outcomes were worse (mRS ≥ 2 in 34.1% vs. 21.9%, p = 0.012) among patients with ruptured aneurysms. CONCLUSION/CONCLUSIONS:Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.

Young adults with hip pathology present a therapeutic challenge requiring careful consideration of treatment options that will affect decades of future function. Historically, the orthopedic community has maintained a strong preservation bias, often pursuing multiple preservation attempts before considering arthroplasty because of concerns about implant longevity. This narrative review critically examines current evidence regarding hip preservation surgery and total hip arthroplasty in young adults to inform evidence-based decision making. The literature reveals that successful hip preservation requires a narrow therapeutic window defined by preserved articular cartilage, accurate structural diagnosis, and appropriate patient selection. Clinical and imaging predictors, including joint space narrowing below 2 mm, Tönnis grade 2 or higher osteoarthritis, bipolar chondral damage, and mechanical symptoms, reliably identify patients unlikely to benefit from preservation. Concurrently, advances in bearing surfaces-particularly highly cross-linked polyethylene and ceramics-have dramatically improved arthroplasty outcomes, with contemporary data demonstrating 10-year survivorship exceeding 90% in patients younger than 55 years. Modern total hip arthroplasty delivers consistent pain relief and functional improvement that often exceeds preservation outcomes in appropriately indicated patients. This review proposes a decision-making framework emphasizing that treatment selection should be guided by objective disease characteristics rather than age-based algorithms, optimizing long-term outcomes while minimizing unnecessary morbidity.