Citations

Background. Ex vivo machine perfusion (MP) has transformed organ preservation, offering significant benefits in liver transplantation (LT), particularly with high-risk donor grafts. However, adoption in the United States has been limited. We aimed to examine early adoption trends, surgeon perceptions, and barriers to implementing MP in the United States after Food and Drug Administration approval of MP platforms. Methods. A 23-question electronic survey was distributed to members of the American Society of Transplant Surgeons between October and November 2022, capturing attitudes and practices related to MP adoption. Responses from 96 surgeons representing 77 LT centers across 11 Organ Procurement and Transplantation Network regions were analyzed. Results. Forty-four respondents (48%) reported having an MP program at their institution. Adoption of MP was significantly more common in high-volume centers and those performing ≥20 donation after circulatory death (DCD) transplants annually (P < 0.001). MP utilization received strong support, with 88% endorsing its use for DCD liver allografts and 82% for donation after brain death allografts. Respondents cited MP’s ability to reduce ischemic cholangiopathy, enable graft repair, and facilitate viability assessment as key benefits. Normothermic MP was preferred for high-risk donor profiles, including DCD grafts, older donors, and steatotic livers, and was associated with an increased willingness to accept medically complex grafts compared with static cold storage. Barriers to MP utilization included program costs, personnel demands, and logistical complexities. Centers with higher proportions of privately insured patients were more likely to adopt MP. Despite these challenges, 84% of respondents expressed interest in future MP adoption. Conclusions. MP enhances graft utilization and outcomes, particularly for complex and high-risk donor livers, but widespread US adoption requires addressing financial and logistical barriers. Future efforts should focus on refining cost-effectiveness analyses, collaboration with organ procurement organizations and device companies, and developing standardized training to optimize MP integration and maximize its clinical impact on LT.

PURPOSE Automated curation of breast cancer treatment data with minimal human involvement could accelerate the collection of statewide and nationwide evidence for patient management and assessing the effectiveness of treatment pathways. The primary challenges are the complexity and inconsistency of structured clinical data streams and accurate extraction of this information from free-text clinical narratives. MATERIALS AND METHODS We proposed a hybrid two-phase information extraction framework that combined a Unified Medical Language System parser (phase-1) with a fine-tuned large language model (LLM; phase-2) to extract longitudinal treatment timelines from time-stamped clinical notes. Our framework was developed through end-to-end joint learning as a question-answering model, where the model was trained to simultaneously answer five questions, each corresponding to a specific treatment. RESULTS We fine-tuned and internally validated the model on 26,692 patients with breast cancer (diagnosed between 2013 and 2020) receiving treatment at Mayo Clinic and externally validated the model on 162 randomly selected patients from Stanford Healthcare. Zero-shot LLM (out-of-the-box) had high specificity but low sensitivity, indicating that although these frameworks are useful for generic language understanding, they are lacking in terms of targeted clinical tasks. The proposed model achieved 0.942 average AUROC on the internal and 0.924 on the external data, demonstrating only marginal drop in performance when evaluated on external. The proposed model also achieved better trade-off between sensitivity (average: 79.2%) and specificity (average: 76.2%) compared with rule-based (average sensitivity: 70.5%, average specificity: 68.1%) and structured codes (average sensitivity: 64.1%, average specificity: 83.5%). CONCLUSION The proposed framework can extract temporal information about cancer treatments from various time-stamped clinic notes, regardless of the setting of treatment administration (inpatient or outpatient) or time frame. To support the cancer research community for such data curation and longitudinal analysis, we have packaged the code as a docker image, which needs minimal system reconfiguration and shared with an open-source academic license.

Abstract Background We examined how the COVID-19 pandemic influenced influenza vaccination, healthcare engagement, and patient satisfaction. Methods We retrospectively analyzed influenza vaccination records and patient experience surveys of adult primary care patients in southeastern Minnesota during two 3-year phases: Prepandemic (1 January 2017–28 February 2020) and Pandemic-Plus (1 March 2020–31 December 2023). Vaccination status was defined as “always vaccinated” (AV), “never vaccinated” (NV), or “intermittently vaccinated” (IV) for seasonal influenza. Results During the Pandemic-Plus phase, 7.0% (n = 3556) of the Prepandemic AV and 48.7% (n = 16 710) of the Prepandemic IV patients never received another influenza vaccine. Compared to AV, IV and NV patients were more likely to reside in areas with greater socioeconomic deprivation (odds ratio [OR], 1.58 [95% confidence interval {CI}, 1.53–1.62] and 1.99 [1.94–2.05], respectively), have a high school education or less (2.86 [2.74–2.98] and 3.38 [3.23–3.53]), and report healthcare disengagement (1.59 [1.55–1.64] and 4.21 [4.09–4.33]). After adjusting for Area Deprivation Index and medical comorbidities, healthcare disengagement increased among the NV versus AV between phases (3.33 [3.24–3.41] and 4.23 [4.10–4.35]). In a subgroup analysis those with severe comorbidities were less likely AV (NV vs AV: 1.21 [1.14–1.27]) and more dissatisfied with care (NV vs AV: 1.25 [1.18–1.33]). Conclusions The COVID-19 pandemic altered vaccination behaviors and healthcare satisfaction, especially among those at high risk of developing influenza-related complications. Medical providers and public health officials should be aware of factors associated with vaccine refusal to better target interventions.

PURPOSE Despite international medical graduates (IMGs) accounting for up to one third of all practicing oncologists in the United States, and nearly half of fellowship trainees, little is known about their contributions to presentations at international oncology meetings. Therefore, we investigated the representation of IMGs in invited faculty roles at the ASCO Annual Meeting as a representative example. METHODS Presentation data from ASCO 2022 and 2023 Annual Meetings were obtained from program guides. We collected presentation-level and speaker-level variables of invited faculty roles and original research. Speakers were categorized as American medical graduate (AMG), IMG, non–US-based, or non-MD (Doctor of Medicine). Univariable and multivariable analyses assessed factors influencing selection for invited faculty roles. RESULTS A total of 2,590 presentations by 2,109 unique speakers were reviewed, including primary research presenters and invited faculty. Among the 1,352 presentations by AMGs, 30% were primary research and 70% were invited faculty roles. For the 374 presentations by IMGs, 41% were primary research and 59% were invited faculty roles. Notably, first-author IMGs were significantly less likely to receive invited faculty roles relative to their primary research output compared with first-author AMGs (adjusted odds ratio, 0.69 [95% CI, 0.53 to 0.90]; P = .006), even when accounting for academic rank, presumed sex, and year. CONCLUSION Relative to IMGs' original research output, IMGs appear to receive fewer invitations for ASCO Annual Meeting invited faculty roles compared with AMGs. Our findings suggest potential underrepresentation and under-recognition of IMGs in these roles, despite their contributions to the oncology workforce in the United States.

Abstract Aggregation and nuclear depletion of the RNA binding protein TDP-43 are the crucial pathological features of amyotrophic lateral sclerosis (ALS) and inclusion body myositis (IBM), two degenerative diseases of the CNS and muscle. The loss of TDP-43 nuclear function results in the aberrant inclusion of cryptic exons in mRNA transcripts, leading to the expression of de novo proteins. Clonally expanded and highly differentiated CD8 + T cells have been observed in individuals with TDP-43 proteinopathies and therapeutics modulating the T cell response have recently been found to extend survival. However, the target antigens mediating T cell activation have remained elusive. Here, we investigate whether the de novo proteins induced by aberrant cryptic splicing due to TDP-43 nuclear loss can act as neo-antigens. We detect the HDGFL2 cryptic peptide and multiple other TDP-43 cryptic exons in IBM skeletal muscle, where their presence correlates with enrichment of T cells and class I antigen presentation pathways. Furthermore, we identify epitopes deriving from HDGFL2 and IGLON5 cryptic peptides which are recognized by clonally expanded and functionally differentiated populations of CD8 + T cells in ALS and IBM Patients. Finally, we demonstrate that T cells engineered to express the identified TCRs can bind and activate in response to the cryptic peptide derived epitopes (cryptic epitopes) and are able to kill TDP-43 deficient astrocytes. This work identifies for the first time specific T cell antigens in ALS and IBM, directly linking adaptive immune response to TDP-43 pathology.

Abstract Introduction Endogenous Cushing's syndrome (CS) is a rare endocrine disorder that chronically exposes patients to supraphysiological cortisol levels. Primary therapy for CS consists of surgery. Medical therapies are also considered for many patients with CS, including those who are not surgical candidates or have persistent or recurrent hypercortisolism after surgery. Osilodrostat, an adrenal steroidogenesis inhibitor, demonstrated sustained efficacy and safety in phase 3 clinical trials and is currently approved to treat endogenous CS in Europe and the United States. Because of limited clinical experience, questions remain about how to individualize osilodrostat treatment for different clinical scenarios and special populations. Additional guidance from experts based on clinical study and real-world experiences with osilodrostat is needed. Methods A modified Delphi consensus panel study was conducted consisting of 13 specialists from high-volume endocrinology centers with experience prescribing osilodrostat. Advisors participated in 3 consensus rounds (2 anonymous surveys, 1 virtual workshop) over approximately 10 months to provide guidance and recommendations on optimal osilodrostat use. Results Over 2 surveys and a 2-hour virtual workshop, 26 statements related to osilodrostat achieved consensus among Delphi panelists and 5 were excluded. Topics included patient preparation before osilodrostat initiation, baseline testing, dosing at onset and during treatment, managing dose adjustments, monitoring during dose titration, and treatment alterations for planned and unexpected clinical events. Conclusion Treatment guidance and recommendations for osilodrostat use were obtained using the Delphi method. These statements are intended to provide physicians with education and guidance on using osilodrostat to optimally treat patients with CS.

Coeliac disease is characterised by immune-mediated damage to the small intestine in response to dietary gluten in genetically predisposed individuals. Increased intestinal permeability is a central component to its pathophysiology. This review explores the evidence for increased permeability in coeliac disease and the underlying mechanisms, including the roles of zonulin, inflammatory cytokines, microbial alterations and immune responses to gliadin peptides. We also review comprehensively the therapies targeting barrier integrity and normalising intestinal permeability, including particular diets and supplements, and experimental and improved medications including larazotide acetate and IMU-856. Finally, we highlight the need for reliable biomarkers for evaluating increased permeability in coeliac disease and advocate for further research on therapies which normalise barrier function, particularly as a strategy to maintain remission.

Abstract Acute appendicitis is a common surgical emergency, most often caused by luminal obstruction from fecaliths. Rarely, foreign body ingestion can lead to appendicitis, particularly when small objects like lead shot become lodged in the appendix. We present the case of a 30-year-old man with chronic intermittent right lower quadrant pain who presented with an acute exacerbation. Imaging revealed two metallic densities in the appendix without overt signs of inflammation. He underwent laparoscopic appendectomy, which confirmed the presence of two retained lead pellets and histologic evidence of acute appendicitis. The patient had a history of frequent game meat consumption. This case underscores a rare but important etiology of appendicitis and the potential for systemic lead exposure from retained foreign bodies. In patients with relevant social histories and suggestive imaging, clinicians should consider this diagnosis and proceed with timely surgical management to prevent complications.