Citations

Increased shear, pressure, and oxygen tension in vein grafts may alter production of endothelium-derived vasoactive and anti-mitogenic factors such as nitric oxide which subsequently affect development of neointimal hyperplasia. This study was designed to determine whether or not nitric oxide mediates endothelium-dependent responses in femoral in situ vein grafts. Non-reversed, canine femoral vein grafts were placed bilaterally to bypass a ligated segment of the femoral artery in dogs. After 6 weeks, the grafts were removed, cut into rings, and suspended in organ chambers for measurement of isometric force. In some rings the endothelium was removed deliberately. In the presence of indomethacin, the synthetic analog of L-arginine, L-NG-monomethyl-arginine (10−4 M: L-NMMA) did not cause a significant change in baseline tension of rings with endothelium. L-NMMA reduced only contractions of rings with endothelium to the alpha-adrenergic agonist UK 14,304. The analog also reduced maximal relaxations to the calcium-ionophore, A23187 in rings with endothelium. In addition, L-NMMA reduced relaxations of rings without endothelium to adenosine diphosphate by 35%. Positive immunostaining for nitric oxide synthase was present in both the myointima and media of histological sections of grafts. In conclusion, these results suggest that in situ vein grafts exhibit two unique properties which are unlike unoperated arteries or veins: (i) alpha2-adrenergic receptors may be coupled to the release of contractile endothelium-derived factors associated with production of nitric oxide; and (ii) nitric oxide may be released by the smooth muscle in response to purinergic stimulation. The presence of nitric oxide synthase throughout the wall of the graft may result in production of nitric oxide in response to adenosine diphosphate released by platelets and to circulating catecholamines.

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended to encourage question-asking by patients and enhance patient-physician communication. To date, an EoE-specific QPL has not been developed for EoE patients. Aim: To develop a preliminary QPL specific to adults with EoE by incorporating input from international esophageal experts. Methods: Sixteen experts were invited to generate QPL content through a modified Delphi (RAND/University of California, Los Angeles, CA) method consisting of 2 rounds of independent ratings. In round 1, experts provided 5 answers to the prompts “what general questions should patients ask when being seen for EoE?” and “what questions do I not hear patients asking but given my experience, I believe they should be asking?” In round 2, experts rated each question on a 5-point Likert scale, and responses rated as “essential” or “important” (determined by an a priori median threshold of ≥ 4.0) were accepted for the EoE QPL. Results: Ten esophageal experts participated in both rounds. Round 1 generated 100 questions. Questions were combined and modified to reduce redundancy, yielding 57 questions. After round 2, 51 questions (85%) were accepted for inclusion (median value ≥ 4.0) in the final QPL. Questions were then divided into 4 themes based on disease domains: (1) “What is EoE?,” (2) “Treatment Options,” (3) “Follow-up Surveillance and Long-term Risks,” and (4) “Allergy and Genetic Testing.” The largest number of questions covered was “What is EoE?” (16/51 or 31%). Questions with the highest agreement median (5.0) included examples such as “what should I do if I get a food impaction?” and “what are the treatment options?” Conclusion: This is the first preliminary EoE QPL developed in the field of medicine. We hope implementation enhances effective patient-physician communication by encouraging patients to ask relevant questions that experts prioritized. Future studies will aim to modify this communication tool by incorporating patient perspectives

Purpose: To analyze the accuracy and thoroughness of three large language models (LLMs) to produce information for providers about immune checkpoint inhibitor ocular toxicities. Methods: Eight questions were created about the general definition of checkpoint inhibitors, their mechanism of action, ocular toxicities, and toxicity management. All were inputted into ChatGPT 4.0, Bard, and LLaMA programs. Using the six-point Likert scale for accuracy and completeness, four ophthalmologists who routinely treat ocular toxicities of immunotherapy agents rated the LLMs answers. Analysis of variance testing was used to assess significant differences among the three LLMs and a post hoc pairwise t-test. Fleiss kappa values were calculated to account for interrater variability. Results: ChatGPT responses were rated with an average of 4.59 for accuracy and 4.09 for completeness; Bard answers were rated 4.59 and 4.19; LLaMA results were rated 4.38 and 4.03. The three LLMs did not significantly differ in accuracy (P = 0.47) nor completeness (P = 0.86). Fleiss kappa values were found to be poor for both accuracy (−0.03) and completeness (0.01). Conclusion: All three LLMs provided highly accurate and complete responses to questions centered on immune checkpoint inhibitor ocular toxicities and management. Further studies are needed to assess specific immune checkpoint inhibitor agents and the accuracy and completeness of updated versions of LLMs.

Background: Surgical management of failed metacarpophalangeal (MCP) arthroplasties includes revision arthroplasty and arthrodesis. The purpose of this study was to review the indications and outcomes of arthrodesis as a salvage procedure for failed MCP arthroplasties. Methods: This was a retrospective cohort study of all patients undergoing salvage MCP arthrodesis at a single institution from 1990 to 2020. Patient charts were reviewed for patient demographics, indication for salvage, surgical technique, revision rate, and time to radiographic union. Patient-reported outcomes, including the Michigan Hand Outcomes Questionnaire and an MCP-specific questionnaire detailing pain, functional, appearance, and patient satisfaction, were also collected. Results: Eleven digits in 9 patients (6 women, 3 men, median age of 66) with median 36-month follow-up were included. The majority (91%) of patients also had concomitant soft tissue deformities, including joint contractures, extension lag, and collateral ligament insufficiency. The overall revision rate following arthrodesis was 45% with 3 digits requiring one revision each, and 2 digits undergoing 3 revisions. The overall union rate was 91% with median time to union of 4 months from most recent arthrodesis. Patient-reported outcomes obtained from 4 patients demonstrated improvements in pain and function. Conclusion: Despite a high revision rate of 45%, salvage MCP arthrodesis following arthroplasty has a high eventual union rate of 91% and is associated with improved pain and function based on 4 patients’ experiences. Arthrodesis as a salvage procedure for failed MCP arthroplasties should be considered in patients with persistent joint instability and functionally limiting soft tissue deformities.

Renal fusion or ectopia can present formidable challenges during aortic surgery. To evaluate morbidity and define optimal management, the clinical histories of 120 patients with renal fusion or ectopia who underwent 21 aortic procedures at the authors' institution over a 37-year period were reviewed. Indications for surgery included aortic aneurysm in 16 patients (infrarenal in 15 and thoracoabdominal in one) and aortoiliac occlusive disease in five (with renovascular hypertension in two). The abnormal kidney was detected before surgery in 13 patients (65%) by excretory urography, arteriography, computed tomography, or ultrasonography. Arteriography revealed multiple and/or anomalous renal arteries in nine of 12 patients studied. At surgery, 15 patients (75%) were found to have multiple or anomalous renal arteries. Six required renal revascularization (reimplantation four, endarterectomy one, aortorenal bypass one). The renal symphysis was divided in two patients. There were no operative deaths. Six major complications included bleeding requiring reoperation, renal failure requiring short-term dialysis, pancreatitis, gastrointestinal bleeding, pneumonia and thrombophlebitis. Preoperative aortography is recommended in patients with renal fusion or ectopia because of the high incidence of associated renal artery anomalies. The surgeon must be prepared to preserve or revascularize these anomalous renal arteries. Division of the renal symphysis is rarely required. Although perioperative morbidity is raised, aortic reconstruction in patients with renal fusion or ectopia can be safely performed without increased mortality.

Purpose Optimizing the preparation of a 10 ml syringe for manual injection of contrast media can help operators obtain easier and faster injections. This study aims to compare the flow rates of different contrast media injection methods. Methods Different contrast media solutions were compared: 100% contrast (10 ml contrast), mixed contrast solution (8:2 contrast/saline), and layered contrast below saline (“Parfait”) in different volumes. Contrast media were injected at room temperature (20°C) and after heating (37°C). Four operators injected 10 ml syringes filled with different mediums through 5-French angiographic catheters. The average flow rate was used to compare different contrast injection mediums. The Kruskal-Wallis test with post-hoc pairwise comparisons using Bonferroni correction or Mann-Whitney U-tests were employed depending on the type of comparison. Results Compared to the 100% contrast solution, every Parfait media and mixed contrast solution demonstrated significantly higher flow rates (p < 0.001). The 5 ml saline Parfait had the highest flow rate among the Parfait solutions. The 5 ml saline Parfait and the mixed solution had comparable flow rates (p = 0.237). Higher flow rates were observed upon heating both 100% contrast (p < 0.001) and mixed contrast solutions (p < 0.001) in comparison to their flow rates at room temperature. Conclusion This study demonstrates the capability of the Parfait and mixed contrast injections to achieve higher flow rates than the 100% contrast solutions. Heating the contrast media to 37°C also proves to be a viable strategy for further enhancing the flow rates for 100% and mixed contrast solutions.

ImportanceA subgroup analysis of a randomized clinical trial established the efficacy of selexipag plus background therapy (monotherapy or double oral therapy [DOT]) vs placebo plus background therapy and found that the addition of selexipag within 6 months had an added benefit. However, the timing of selexipag addition to DOT and the incremental benefit in clinical practice is not well studied.ObjectiveTo compare triple oral therapy (TOT) consisting of selexipag, endothelin receptor antagonist (ERA), and phosphodiesterase type 5 inhibitor (PDE5i) vs DOT consisting of ERA and PDE5i.Design, Setting, and ParticipantsThis comparative effectiveness study was conducted using data from the US Komodo claims database to emulate a randomized trial. Patients aged 18 years or older with pulmonary arterial hypertension (PAH) treated with ERA plus PDE5i with records from July 2015 through June 2022 were duplicated to TOT and DOT and artificially censored when observed treatment deviated from assigned treatment. Hypothetical randomization was emulated using inverse probability of treatment weighting, and the study accounted for censoring-induced selection bias using inverse probability of censoring weighting. A pooled logistic model estimated the per-protocol difference between treatment groups. Data were analyzed from November 2022 through July 2023.InterventionsTOT (addition of selexipag within 3, 6, and 12 months of initiating DOT) vs DOT.Main Outcomes and MeasuresAdjusted risk of all-cause hospitalization, PAH-related hospitalization, and PAH-related disease progression over a 2-year follow-up.ResultsA total of 2966 patients with PAH (mean [SD] age, 54.3 [14.0] years; 2125 female [71.6%]) met eligibility criteria. Adding selexipag within 6 months of ongoing DOT was associated with a reduction in risk for all-cause hospitalization (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.72-0.94), PAH-related hospitalization (aHR, 0.81; 95% CI, 0.70-0.95), and PAH-related progression (aHR, 0.82; 95% CI, 0.70-0.95) vs DOT alone. There were no associations if selexipag was initiated within 12 months for all-cause hospitalization, PAH-related hospitalization, or PAH-related disease progression. The association remained with a greater decrease in risk for disease progression vs DOT for selexipag initiation within 3 months (aHR, 0.74; 95% CI, 0.61-0.90).Conclusions and RelevanceThis study found that early selexipag addition to ERA plus PDE5i was associated with a reduction in risk of hospitalization and disease progression. These findings suggest that delays in selexipag initiation likely contribute to suboptimal patient and health system outcomes.

ImportancePatients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT.ObjectiveTo compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT.Design, Setting, and ParticipantsThis cohort study was a propensity score–matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score–matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score.ExposureLeft atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group).Main Outcomes and MeasuresThe primary outcome was time to first ischemic stroke.ResultsFour hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P &amp;lt; .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy.Conclusions and RelevanceIn patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.