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OBJECTIVES: Current research does not address the existence and impact of structured tele-critical care (TCC) training on the delivery of care in the ICU. This pilot study aimed to evaluate the association between on boarding elements focused on training and clinicians perceptions of delivery of care. DESIGN: Cross-sectional survey study. SETTING AND PARTICIPANTS: Critical Care professionals at four U.S. hospitals, professional meetings and Society of Critical Care Medicine’s International Membership base. Participants were active clinicians who practice in the TCC setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 432 participants responded to the survey, 227 met the eligibility criteria (52.5%) and were included in the analysis. Respondents were a multi-professional group of TCC clinicians aged between 35–55 years of age (56.4%). Seventy-four percent of respondents reported having orientation before providing TCC, 46% reported having formal mentorship, and 66% reported formal training on their institutional platform. Provision of orientation before participating in a TCC program was associated with higher ratings of feeling prepared (odds ratio [OR], 3.52; p < 0.001) and feeling accepted as part of the ICU team (OR, 2.21; p = 0.008). Mentorship was associated with feeling more prepared (OR, 8.2; p < 0.001) and higher comfort in delivering care (OR, 2.78; p = 0.016). Platform training was associated with feeling more prepared (OR, 4.66; p < 0.001), comfortable in delivering care (OR, 3.6; p = 0.002), feeling accepted as part of the team (OR, 3.18; p < 0.001), and more likely to participate in quality improvement (OR, 2.51; p = 0.001). A site visit also made a positive impact in feeling prepared (OR, 2.86; p < 0.001), comfortable (OR, 4.95; p = 0.002), feeling like recommendations were accepted (OR, 3.73; p < 0.001), more likely to recommend TCC (OR, 3.18; p = 0.001), and participating in quality improvement (OR, 3.24; p < 0.001). CONCLUSIONS: In this pilot study, structured training utilizing orientation, mentorship, and platform training as surrogates, along with a site visit before beginning delivery of care in a TCC setting, were associated with more positive perceptions in the delivery of care domains assessed. We highlight potentially important factors that warrant further evaluation and assessment of the need for standardization across TCC programs.

Importance Emergency department (ED) visits for people with dementia often involve care (including the admission or discharge decision) with lasting effects on quality of life. Home time—a claims-based measure of days alive and outside of institutional care—provides a patient-centered way to assess downstream outcomes of ED care in this population. Objective To examine variations in home time following an ED visit by patient, facility, and visit characteristics among veterans with dementia. Design, Setting, and Participants This national retrospective cohort study used US Department of Veterans Affairs (VA) health care system data sources. Participants were veterans aged 65 to 110 years with dementia with an eligible Veterans Health Administration ED visit in fiscal years 2017 (October 1, 2016, through September 30, 2017) and/or 2018 (October 1, 2017, through September 30, 2018). Data were analyzed from May 1, 2024, to May 15, 2025. Exposures Patient, ED facility, and ED visit factors. Main Outcomes and Measures Home time, operationalized for modeling as days not at home in the 180 days after the index ED visit. Associations between patient, ED facility, and ED visit characteristics and home time were assessed using a negative binomial model. Results The study included 51 707 veterans with dementia (mean [SD] age, 79.9 [8.59] years; 97.6% male; 52.2% married). The mean (SD) number of days not at home within 180 days was 21.7 (34.5). Of the total cohort, 4.5% never returned home in the 180 days after their ED visit, while 18.2% had all subsequent days at home. ED admission (vs discharge) disposition was the factor associated with the largest increase in days not at home (rate ratio [RR], 3.18; 95% CI, 3.08-3.29). Patient factors associated with more days not at home included very high frailty (RR, 1.27; 95% CI, 1.21-1.33), unhoused status (RR, 1.50; 95% CI, 1.39-1.63), unmarried status (never married: RR, 1.24 [95% CI, 1.16-1.32]; divorced, separated, or widowed: RR, 1.24 [95% CI, 1.20-1.28]), and depression (RR, 1.13; 95% CI, 1.09-1.17). Conclusions and Relevance The findings of this cohort study suggest that home time offers a patient-centered measure of post-ED outcomes for individuals with dementia. Future work should refine its application, particularly regarding the ED disposition decision, to better evaluate the long-term impact of ED care decisions.

Purpose: Irreversible corneal blindness disproportionately affects low- and middle-income countries where there remains a critical demand for surgeons skilled in corneal transplantation. Penetrating keratoplasty (PK) is a critical skill for ophthalmologists, especially as it remains the most widely performed type of corneal transplant in these parts of the world. Tools to teach and assess trainees in corneal transplantation are needed to help standardize training internationally. Here, we present an Ophthalmology Surgical Competency Assessment Rubric (OSCAR) aimed at assessing the competence and progress of residents in PK. Methods: A team of cornea specialists developed a rubric for PK using previously published OSCARs as a template. The draft included 11 key steps of PK and six global indices, with a grading scale based on a modified Dreyfus model. The rubric was then reviewed for face and content validity by a panel of eight international experts using an iterative feedback process. The draft underwent multiple cycles of feedback and revisions until a consensus was reached among the authors and the international expert panel. Results: The rubric contains 11 essential steps and six global indices with descriptions of expected functioning at four levels of competency (novice, beginner, advanced beginner, and competent). Conclusions: This OSCAR for PK contributes to the global standardization of ophthalmology training, helping to meet the increasing demand for corneal transplant services with high-quality care for all.

Abstract Purpose: Mutant IDH1 (mIDH1) defines a therapeutically targetable subtype of intrahepatic cholangiocarcinoma (ICC), with the mIDH1 inhibitor ivosidenib approved for advanced disease. A subset of patients experiences prolonged disease stabilization; however, the molecular basis for eventual progression remains poorly defined. Experimental Design: We performed molecular profiling of matched baseline and postprogression circulating tumor DNA (ctDNA) samples from patients with mIDH1 ICC enrolled in the ClarIDHy phase III trial. Functional studies were conducted to characterize candidate resistance mechanisms. Results: Longitudinal ctDNA analysis of 18 patients treated with ivosidenib for &gt;6 months revealed emergent genomic alterations in multiple cases. Acquired mutations in mitogen-activated protein kinase (MAPK) pathway genes (KRAS, NRAS, MAP2K1, NF1) were identified in five cases, with instances of concurrent alterations and/or high variant allele fractions (VAF). Additional candidate resistance events included a secondary IDH1 mutation and a hotspot IDH2 mutation, detected at low VAF in the same patient. Functional studies showed that these IDH mutations conferred sustained 2-hydroxyglutarate production and ivosidenib resistance, whereas MAPK activation blunted gene expression induced by ivosidenib plus IFNγ, a key therapeutic output of mIDH1 inhibition. In parallel, baseline ctDNA profiling of 81 patients revealed that ARID1A mutations and elevated mIDH1 VAF were associated with reduced clinical benefit. Conclusions: MAPK pathway alterations represent a recurrent mechanism of resistance to mIDH1 inhibition in ICC, whereas emergent IDH1/IDH2 mutations appear infrequent. Functional data suggest that MAPK-mediated resistance may involve impaired IFN signaling. These results support MAPK-directed combination strategies and highlight the utility of ctDNA profiling to identify predictive and resistance biomarkers in mIDH1-driven ICC.

BACKGROUND AND OBJECTIVES: Anterior lumbar interbody fusion (ALIF) is a powerful procedure for sagittal correction and indirect decompression in the lumbar spine, though aggressive correction can cause stretch neuropraxia and implant subsidence. The aim of this study was to identify radiographic and clinical predictors of segmental correction, as well as to evaluate the degree to which segmental correction on supine intraoperative radiographs translates to postoperative upright alignment changes. METHODS: We identified patients treated with 1- or 2-level ALIF at a tertiary care center and extracted data on demographics, spinopelvic parameters, and surgical details. Patients treated with isolated ALIF and ALIF with supplementary posterior instrumentation were compared on pre- and postoperative intradiscal lordosis (IDL) and change in IDL. Multivariable linear regression was performed to identify independent predictors of postoperative IDL. RESULTS: We included 204 patients (median age 57 years, 55.4% male) treated at 258 levels, of whom 114 (55.9%) underwent supplementary posterior fixation and 150 (73.5%) underwent single-level implantation. Across all patients, postoperative IDL was significantly greater than preoperative segmental lordosis (25.4° vs 15.3°; P < .001). Standalone ALIF achieved less ΔIDL than circumferential fusion for L5/S1 procedures (7.4° vs 11.6°; P < .001), though ΔIDL for L3/4 and L4/5 was similar between the standalone and circumferential groups. Multivariable analysis showed postoperative IDL to be predicted by greater preoperative IDL (β = 0.26° per degree; [0.15, 0.36]; P < .001), L5/S1 [vs L4/5] implantation (β = 3.97°; [2.72, 5.21]; P < .001), use of supplementary posterior fixation (β = 1.80°; [0.70, 2.89]; P < .001), and greater implant lordosis (β = 0.62° per degree; [0.44, 0.79]; P < .001). CONCLUSION: Postoperative IDL after 1- or 2-level ALIF is best predicted by placement of larger interbody sizes, L5/S1 implantation, greater baseline IDL, and use of adjunct posterior fixation. Patients with higher preoperative lordosis experienced smaller postoperative increases in IDL, though this was likely influenced by a treatment bias.

Abstract Background Immunohistochemically detected phosphorylated α‐synuclein (p‐α‐syn) in cutaneous nerves has been found in >95% of patients meeting consensus criteria for dementia with Lewy bodies (DLB); however, its performance in prodromal stages (mild cognitive impairment‐Lewy body [MCI‐LB]) and clinical practice is unknown. Objective We evaluated skin biopsy for p‐α‐syn in a convenience cohort of patients with suspected MCI‐LB or DLB in a tertiary care setting. Methods 53 patients underwent commercially available skin biopsy for skin nerve p‐α‐syn as part of a clinical evaluation for suspected MCI‐LB/DLB. Consensus MCI‐LB/DLB criteria blinded to skin biopsy result were applied through retrospective chart review; those not definitively meeting criteria were considered questionable synucleinopathy (QS). Results Median age at skin biopsy was 70 years (range, 43–87 years) with 81% men. 36 patients (68%) had positive skin biopsies. 32/43 (74%) patients meeting clinical consensus criteria for DLB/MCI‐LB had a positive skin biopsy, with higher frequency in MCI‐LB (87%) compared with DLB (60%). 4/10 (40%) QS had positive biopsies. One patient with a positive skin biopsy had no evidence of central nervous system (CNS) α‐syn on autopsy. Conclusions Positive skin biopsy for p‐α‐syn occurs across the spectrum of cognitive presentations of Lewy body disease including prodromal DLB, albeit at a lower frequency in this retrospective review of atypical cases compared with typical clinical presentations. A positive skin biopsy may not reflect CNS synucleinopathy as the etiology for a patient's symptoms in some cases. Longitudinal studies of skin biopsies for p‐α‐syn in suspected MCI‐LB/DLB with autopsy confirmation are needed. © 2025 International Parkinson and Movement Disorder Society.

Abstract Molecular profiling of human primary cell types is essential for understanding human biology. We present a transcriptome and proteome map of 28 primary human cell types. Three major clusters of epithelial, endothelial, and mesenchymal cell types were observed in both the transcriptome and proteome levels along with the discovery of cell type enriched molecules including GRAP and C1orf116. The epithelial cell specific protein C1orf116 was further validated using immunohistochemistry across various human tissues. An exhaustive protein database search considering 39 post-translational modifications (PTMs) revealed novel insights into the PTM landscape including identification of understudied PTMs such as serine O-acetylation and histidine methylation. This also enabled comprehensive characterization of proteins with diverse PTMs. Interestingly, an unexpectedly higher frequency of dioxidation on tryptophan compared to methionine led to the identification of oxidative mitochondria complex subunit proteins. Further, a search strategy accounting for alternative translational start sites, splice junctions and translational readthrough refined genome annotation using proteomic evidence. For example, peptides from translational readthrough including extended sequence of LDHB and MDH1 were detected representing the first peptide-level evidence of these protein readthrough isoforms. Our comprehensive transcriptome and proteome data revealed cell type-specific molecular cues and heterogeneity, offering new insights into disease mechanisms often overlooked by tissue proteomics.

The application of artificial intelligence (AI), large language models and generative AI (GenAI) is accelerating rapidly across many industries worldwide. Innovative models and tools are being piloted to understand their business and societal value. Models such as ChatGPT (OpenAI), Gemini (Google) and Copilot (Microsoft) have become increasingly sophisticated and widely adopted. Understanding the advantages and drawbacks of GenAI models is crucial for organisations seeking to leverage GenAI to maximise their efficiency and expand their capabilities. This paper describes the strategic approach, implementation and findings of using GenAI in a health care business context. A GenAI model was used to analyse and summarise strategic and operational information submitted by external organisations seeking to collaborate with Mayo Clinic. The goal was to reduce process cycle time and manual resource intensity. In parallel, a comparative human review was conducted by functional experts. Both the AI-generated and human-reviewed results were evaluated using sentiment analysis (SA) and then categorised as positive, neutral or negative. Attention was paid to possible inaccuracies and biases associated with the use of the GenAI model. GenAI reduced the manual workload by approximately 20−25 per cent and presented information in a well-structured format. However, the SA showed the GenAI results as positively biased and the human-generated results as neutral. These results were most likely influenced by a positive bias in the input documents, the lack of contextual comparators/ standards in the GenAI model and an inherent bias within the model’s algorithm(s). Additionally, limitations in input size and language translation hindered the GenAI model’s effectiveness. The possibility of AI hallucinations/inaccuracies emphasised the importance of validation by a human expert. Furthermore, carefully formatting the input data enhanced the value and relevance of the GenAI model’s outputs. GenAI has the potential to increase efficiency and alleviate manual burden, but it must be thoughtfully implemented to address inaccuracies, biases and privacy concerns. This article is also included in The Business & Management Collection which can be accessed at https:// hstalks.com/business/.