: The epidemiology of abdominal aortic aneurysm (AAA) disease has been well described over the preceding 50 years. This disease primarily affects elderly males with smoking, hypertension, and a ...positive family history contributing to an increased risk of aneurysm formation. The aging population as well as increased screening in high‐risk populations has led some to suggest that the incidence of AAAs is increasing. The National Inpatient Sample (1993–2003), a national representative database, was used in this study to determine trends in mortality following AAA repair in the United States. In addition, the impact of the introduction of less invasive endovascular AAA repair was assessed. Overall rates of treated unruptured and ruptured AAAs remained stable (unruptured 12 to 15/100,000; ruptured 1 to 3/100,000). In 2003, 42.7% of unruptured and 8.8% of ruptured AAAs were repaired through an endovascular approach. Inhospital mortality following unruptured AAA repair continues to decline for open repair (5.3% to 4.7%, P= 0.007). Mortality after elective endovascular AAA repair also has statistically decreased (2.1% to 1.0%, P= 0.024) and remains lower than open repair. Mortality rates for ruptured AAAs following repair remain high (open: 46.5% to 40.7%, P= 0.01; endovascular: 40.0% to 35.3%, P= 0.823). These data suggest that the numbers of patients undergoing elective AAA repair have remained relatively stable despite the introduction of less invasive technology. A shift in the treatment paradigm is occurring with a higher percentage of patients subjected to elective endovascular AAA repair compared to open repair. This shift, at least in the short term, appears justified as the mortality in patients undergoing elective endovascular AAA repair is significantly reduced compared to patients undergoing open AAA repair.
Background: Surrogates, proxies, and clinicians making shared treatment decisions for patients who have lost decision-making capacity often fail to honor patients’ wishes, due to stress, time ...pressures, misunderstanding patient values, and projecting personal biases. Advance directives intend to align care with patient values but are limited by low completion rates and application to only a subset of medical decisions. Here, we investigate the potential of large language models (LLMs) to incorporate patient values in supporting critical care clinical decision-making for incapacitated patients in a proof-of-concept study. Methods: We simulated text-based scenarios for 50 decisionally incapacitated patients for whom a medical condition required imminent clinical decisions regarding specific interventions. For each patient, we also simulated five unique value profiles captured using alternative formats: numeric ranking questionnaires, text-based questionnaires, and free-text narratives. We used pre-trained generative LLMs for two tasks: 1) text extraction of the treatments under consideration and 2) prompt-based question-answering to generate a recommendation in response to the scenario information, extracted treatment, and patient value profiles. Model outputs were compared with adjudications by three domain experts who independently evaluated each scenario and decision. Results and Conclusions: Automated extractions of the treatment in question were accurate for 88% ( n = 44/50) of scenarios. LLM treatment recommendations received an average Likert score by the adjudicators of 3.92 of 5.00 (five being best) across all patients for being medically plausible and reasonable treatment recommendations, and 3.58 of 5.00 for reflecting the documented values of the patient. Scores were highest when patient values were captured as short, unstructured, and free-text narratives based on simulated patient profiles. This proof-of-concept study demonstrates the potential for LLMs to function as support tools for surrogates, proxies, and clinicians aiming to honor the wishes and values of decisionally incapacitated patients.
Objective Broad application of endovascular aneurysm repair (EVAR) has led to a rapid decline in open aneurysm repair (OAR) and improved patient survival, albeit at a higher overall cost of care. The ...aim of this report is to evaluate national trends in the incidence of unruptured and ruptured abdominal aortic aneurysms (AAAs), their management by EVAR and OAR, and to compare overall patient characteristics and clinical outcomes between these two approaches. Methods A retrospective analysis of the cross-sectional National Inpatient Sample (2000-2010) was used to evaluate patient characteristics and outcomes related to EVAR and OAR for unruptured and ruptured AAAs. Data were extrapolated to represent population-level statistics through the use of data from the U.S. Census Bureau. Comparisons between groups were made with the use of descriptive statistics. Results There were 101,978 patients in the National Inpatient Sample affected by AAAs over the 11-year span of this study; the average age was 73 years, 21% were women, and 90% were white. Overall in-hospital mortality rate was 7%, with a median length of stay (LOS) of 5 days and median hospital charges of $58,305. In-hospital mortality rate was 13 times greater for ruptured patients, with a median LOS of 9 days and median charges of $84,744. For both unruptured and ruptured patients, EVAR was associated with a lower in-hospital mortality rate (4% vs 1% for unruptured and 41% vs 27% for ruptured; P < .001 for each), shorter median LOS (7 vs 2; 9 vs 6; P < .001) but a 27%-36% increase in hospital charges. Conclusions The overall use of EVAR has risen sharply in the past 10 years (5.2% to 74% of the total number of AAA repairs) even though the total number of AAAs remains stable at 45,000 cases per year. In-hospital mortality rates for both ruptured and unruptured cases have fallen by more than 50% during this time period. Lower mortality rates and shorter LOS despite a 27%-36% higher cost of care continues to justify the use of EVAR over OAR. For patients with suitable anatomy, EVAR should be the preferred management of both ruptured and unruptured AAAs.
OBJECTIVE—It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix ...metalloproteinases (MMPs).
METHODS AND RESULTS—Group I experiments were as followselastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the followingabdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase.
CONCLUSIONS—These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.
Tobacco smoke is an established risk factor for thoracic aortic aneurysms and dissections (TAAD). However, little is known about its underlying mechanisms due to the lack of validated animal models. ...The present study developed a mouse model that may be utilized to investigate exacerbation of TAAD formation by mimetics of tobacco smoke. TAADs were created via inducible deletion of smooth muscle cell-specific Tgfbr2 receptors. Using this model, the first set of experiments evaluated the efficacy of nicotine salt (34.0 mg/kg/day), nicotine free base (NFB, 5.0 mg 90-day pellets), and cigarette smoke extract (0.1 ml/mouse/day). Compared with their respective control groups, only NFB pellets promoted TAAD dilation (23±3% vs. 12±2%, P=0.014), and this efficacy was achieved at a cost of >50% acute mortality. Infusion of NFB with osmotic minipumps at extremely high, but nonlethal, doses (15.0 or 45.0 mg/kg/day) failed to accelerate TAAD dilation. Interestingly, costimulation with β-aminopropionitrile (BAPN) promoted TAAD dilation and aortic rupture at dosages of 3.0 and 45.0 mg/kg/day, respectively, indicating that BAPN sensitizes the response of TAADs to NFB. In subsequent analyses, the detrimental effects of NFB were associated with clustering of macrophages, neutrophils, and T-cells in areas with structural destruction, enhanced matrix metalloproteinase- (MMP-) 2 production, and pathological angiogenesis with attenuated fibrosis in the adventitia. In conclusion, modeling nicotine exacerbation of TAAD formation requires optimization of chemical form, route of delivery, and dosage of the drug as well as the pathologic complexity of TAADs. Under the optimized conditions of the present study, chronic inflammation and adventitial mal-remodeling serve as critical pathways through which NFB exacerbates TAAD formation.
Joy and Community in Surgery Upchurch, Gilbert R.
The American surgeon,
08/2023, Letnik:
89, Številka:
8
Journal Article
Recenzirano
My wife Nancy is a voluminous reader of books (you remember the things printed on paper). After 30 years of marriage, it dawned on me that we have never really shared books. Therefore, we decided to ...try and enrich our marriage by exchanging books. I asked her to pick out five books that she enjoyed and share them with me so that we could talk about them and have them “in common.” Incidentally, when I asked my wife to pre-read this article, she said, “you make me sound like a total downer” based on the books she had given me to read. In all honesty, my wife Nancy is the most positive person I know, and my kids are a direct reflection of her positive energy. While she refuted my initial portrayal of the books she shared as they somehow portrayed her in a non-joyful light, I realized that each of those books challenged me to think about finding joy in non-standard communities.
Thoracic aortic diseases, including disease of the descending thoracic aorta (DTA), are significant causes of death in the United States. Open repair of the DTA is a physiologically impactful ...operation with relatively high rates of mortality, paraplegia, and renal failure. Thoracic endovascular aortic repair (TEVAR) has revolutionized treatment of the DTA and has largely supplanted open repair because of lower morbidity and mortality. These Society for Vascular Surgery Practice Guidelines are applicable to the use of TEVAR for descending thoracic aortic aneurysm (TAA) as well as for other rarer pathologic processes of the DTA. Management of aortic dissections and traumatic injuries will be discussed in separate Society for Vascular Surgery documents. In general, there is a lack of high-quality evidence across all TAA diseases, highlighting the need for better comparative effectiveness research. Yet, large single-center experiences, administrative databases, and meta-analyses have consistently reported beneficial effects of TEVAR over open repair, especially in the setting of rupture. Many of the strongest recommendations from this guideline focus on imaging before, during, or after TEVAR and include the following:
In patients considered at high risk for symptomatic TAA or acute aortic syndrome, we recommend urgent imaging, usually computed tomography angiography (CTA) because of its speed and ease of use for preoperative planning. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate).
If TEVAR is being considered, we recommend fine-cut (≤0.25 mm) CTA of the entire aorta as well as of the iliac and femoral arteries. CTA of the head and neck is also needed to determine the anatomy of the vertebral arteries. Level of recommendation: Grade 1 (Strong), Quality of Evidence: A (High).
We recommend routine use of three-dimensional centerline reconstruction software for accurate case planning and execution in TEVAR. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate).
We recommend contrast-enhanced computed tomography scanning at 1 month and 12 months after TEVAR and then yearly for life, with consideration of more frequent imaging if an endoleak or other abnormality of concern is detected at 1 month. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate).
Finally, based on our review, in patients who could undergo either technique (within the criteria of the device's instructions for use), we recommend TEVAR as the preferred approach to treat elective DTA aneurysms, given its reduced morbidity and length of stay as well as short-term mortality. Level of recommendation: Grade 1 (Strong), Quality of Evidence: A (High).
Given the benefits of TEVAR, treatment using a minimally invasive approach is largely based on anatomic eligibility rather than on patient-specific factors, as is the case in open TAA repair. Thus, for isolated lesions of the DTA, TEVAR should be the primary method of repair in both the elective and emergent setting based on improved short-term and midterm mortality as well as decreased morbidity.
OBJECTIVE—Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role ...of IL (interleukin)-1β in the formation of murine experimental AAAs. Here, the hypothesis that IL-1β–induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested.
APPROACH AND RESULTS—NETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry. NETs were detected in human AAAs and were colocalized with IL-1β. In vitro, IL-1RA attenuated IL-1β–induced NETosis in human neutrophils. Mechanistically, IL-1β treatment of isolated neutrophils induced nuclear localization of ceramide synthase 6 and synthesis of C16-ceramide, which was inhibited by IL-1RA or fumonicin B1, an inhibitor of ceramide synthesis. Furthermore, IL-1RA or fumonicin B1 attenuated IL1-β–induced NETosis. In an experimental model of murine AAA, NETs were detected at a very early stage–day 3 of aneurysm induction. IL-1β–knockout mice demonstrated significantly lower infiltration of neutrophils to aorta and were protected from AAA. Adoptive transfer of wild-type neutrophils promoted AAA formation in IL-1β–knockout mice. Moreover, treatment of wild-type mice with Cl-amidine, an inhibitor NETosis, significantly attenuated AAA formation, whereas, treatment with deoxyribonuclease, a DNA digesting enzyme, had no effect on AAA formation.
CONCLUSIONS—Altogether, the results suggest a dominant role of IL-1β–induced NETosis in AAA formation.
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