Independent of their blood pressure lowering effect, ACE inhibitors are thought to reduce vascular inflammation. The clinical relevance of this effect is unclear with the current knowledge. Abdominal ...aortic aneurysms (AAA) are characterized by a broad, non-specific inflammatory response, and thus provide a clinical platform to evaluate the anti-inflammatory potential of ACE inhibitors.
Eleven patients scheduled for open AAA repair received ramipril (5 mg/day) during 2-4 weeks preceding surgery. Aortic wall samples were collected during surgery, and compared to matched samples obtained from a biobank. An anti-inflammatory potential was evaluated in a comprehensive analysis that included immunohistochemistry, mRNA and protein analysis. A putative effect of ACE inhibitors on AAA growth was tested separately by comparing 18-month growth rate of patients on ACE inhibitors (n = 82) and those not taking ACE inhibitors (n = 204). Ramipril reduces mRNA expression of multiple pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF -α, Interferon-Formula: see text, and MCP-1, as well as aortic wall IL-8 and MCP-1 (P = 0.017 and 0.008, respectively) protein content. The is followed by clear effects on cell activation that included a shift towards anti-inflammatory macrophage (M2) subtype. Evaluation of data from the PHAST cohort did not indicate an effect of ACE inhibitors on 18-month aneurysm progression (mean difference at 18 months: -0.24 mm (95% CI: -0.90-0.45, P = NS).
ACE inhibition quenches multiple aspects of vascular inflammation in AAA. However, this does not translate into reduced aneurysm growth.
Nederlands Trial Register 1345.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Identification of diseased and normal parathyroid glands during parathyroid surgery can be challenging. The aim of this study was to assess whether near-infrared (NIR) fluorescence imaging ...using administration of a low-dose Methylene Blue (MB) at the start of the operation could provide optical guidance during parathyroid surgery and assist in the detection of parathyroid adenomas. Methods Patients diagnosed with primary hyperparathyroidism planned for parathyroidectomy were included. Patients received 0.5 mg/kg MB intravenously directly after start of anesthesia. During the operation, NIR fluorescence imaging was performed to identify parathyroid adenomas. Imaging results were compared with a previous published feasibility study in which 12 patients received MB after intraoperative identification of the adenoma. Results A total of 13 patients were included in the current study. In 10 of 12 patients with a histologically proven adenoma, the adenoma was fluorescent. Mean signal to background ratio was 3.1 ± 2.8. Mean diameter of the resected lesions was 17 ± 9 mm (range 5–28 mm). Adenomas could be identified up to 145 minutes after administration, which was the longest timespan until resection. Interestingly, in 3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with a signal to background ratio of 1.8 ± 0.4 were identified using NIR fluorescence imaging. Conclusion Early administration of low-dose MB provided guidance during parathyroidectomy by identifying both parathyroid adenomas and normal parathyroid glands. In patients in whom difficult identification of the parathyroid adenoma is expected or when normal glands have to be identified, the administration of MB may improve surgical outcome.
OBJECTIVE:To explore possibilities to improve morbidity and mortality conferences using advancing insights in safety science.
SUMMARY BACKGROUND DATA:Mortality and Morbidity conferences (M&M) are the ...golden practice for case-based learning. While learning from complications is useful, M&M does not meet expectations for system-wide improvement. Resilience engineering principles may be used to improve M&M.
METHODS:After a review of the shortcomings of traditional M&M, resilience engineering principles are explored as a new way to evaluate performance. This led to the development of a new M&M format that also reviews successful outcomes, rather than only complications. This “quality assessment meeting” (QAM) is presented and the first experiences are evaluated using local observations and a survey.
RESULTS:During the QAM teams evaluate all discharged patients, addressing team resilience in terms of surgeons’ ability to respond to irregularities and to monitor and learn from experiences. The meeting was feasible to implement and well received by the surgical team. Observations reveal that reflection on both complicated and uncomplicated cases strengthened team morale but also triggered reflection on the entire clinical course. The QAM serves as a tool to identify how adapting behavior led to success despite challenging conditions, so that this resilient performance can be supported.
CONCLUSIONS:The resilience engineering concept can be used to adjust M&M, in which learning is focused not only on complications but also on how successful outcomes were achieved despite ever-present challenges. This reveals the actual ratio between successful and unsuccessful outcomes, allowing to learn from both to reinforce safety-enhancing behavior.
ObjectiveTo explore what information sources medical specialists currently use to inform their medical decision-making.DesignQualitative, semistructured interviews.Setting and participantsA total of ...20 semistructured interviews were conducted with 10 surgeons and 10 internal medicine specialists who work in academic and/or regional hospitals in the Netherlands.ResultsMedical specialists reported that they primarily rely on their general knowledge and experience, rather than actively using information sources. The sources they use to update their knowledge can be categorised into ‘scientific publications’, ‘guidelines or protocols’, and ‘presentations and meetings’. When medical specialists feel their general knowledge and experience are insufficient, they use three different approaches to find answers in response to clinical questions: consulting a colleague, actively searching the literature and asking someone else to search the literature.ConclusionMedical specialists use information sources to update their general knowledge and to find answers to specific clinical questions when they feel their general knowledge and experience are insufficient. An important finding is that medical specialists prefer accessible information sources (eg, consulting colleagues) over existing evidence-based medicine tools.
OBJECTIVE—Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as ...mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression.
APPROACH AND RESULTS—Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4/CD25/Foxp3 (forkhead box P3) regulatory T cells, with fewer CD8/GZMB (granzyme B) cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)–positive alternatively activated macrophages. These results concurred with gene expression analysis of lipopolysaccharide-stimulated and Ang II-primed human peripheral blood mononuclear cells.
CONCLUSIONS—Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression.
Abstract
Objective
To discuss practical strategies to consider for morbidity and mortality conferences (M&M).
Materials and Methods
This article reflects on (i) insights that can be drawn from the ...M&M literature, (ii) practical aspects to consider when organizing M&M, and (iii) possible future directions for development for this long-standing practice for routine reflection.
Results
M&M offers the opportunity to learn from past cases in order to improve the care delivered to future patients, thereby serving both educational and quality improvement purposes. For departments seeking to implement or improve local M&M practice, it is difficult that a golden standard or best practice for M&M is nonexistent. This is partly because comparative research on different formats is hampered by the lack of objective outcome measures to evaluate the effectiveness of M&M. Common practical suggestions include the use of (i) a skillful and active moderator; (ii) structured formats for case presentation and discussion; and (iii) a dedicated committee to guide improvement plans that ensue from the meeting. M&M practice is affected by various sociological factors, for which qualitative research methods seem most suitable, but in the M&M literature these are sparsely used. Moreover, aspects influencing an open and blame-free atmosphere underline how local teams should tailor the format to best fit the local context and culture.
Conclusion
This article presents practice guidance on how to organize and carry out M&M This practice for routine reflection needs to be tailored to the local setting, with attention for various sociological factors that are at play.
Nutcracker syndrome (NCS) is an uncommon syndrome that presents with signs and symptoms caused by compression of the left renal vein (LRV), whereas ‘nutcracker phenomenon’ is solely used to refer to ...the anatomical configuration without clinical symptoms. Treatment for NCS may include nonoperative management, open surgical intervention, and in some instances endovascular stenting. We present a single-center retrospective case series of patients who presented with NCS managed with open surgical interventions.
A single-center, retrospective review of patients managed from 2010–2021. We diagnosed NCS via a thorough clinical examination and additional cross-sectional imaging studies including magnetic resonance venography and/or computed tomography venography. For further confirmation of the diagnosis, duplex ultrasound was frequently combined with contrast venography.
Thirty eight patients were included in our study from 2010–2021. Twenty one (55.3%) patients presented with symptoms including flank pain, abdominal pain, hematuria, and fatigue. The remaining 17 (44.7%) patients had nutcracker phenomenon. Within the group of patients diagnosed with NCS, 11 patients underwent LRV transposition. Symptoms related to NCS improved in 10 patients. Hematuria in 1 patient did not improve.
Transposition of the LRV is an effective treatment for NCS. Nonoperative management is an option for those patients experiencing less severe or nonspecific clinical symptoms.
•Duplex ultrasound in combination with venography and MRV/CTV should be the golden standard for examination of NCS.•Transposition of the LRV is an effective treatment for NCS.•Conservative treatment can be a good option for patients experiencing less severe or nonspecific NCS symptoms.
OBJECTIVE:To investigate a new composite quality measurement, which comprises a desirable outcome for elective aneurysm surgery, called “Textbook Outcome” (TO).
BACKGROUND:Single-quality indicators ...in vascular surgery are often not distinctive and insufficiently reflect the quality of care.
METHODS:All patients undergoing elective abdominal aortic aneurysm repair, registered in the Dutch Surgical Aneurysm Audit between 2014 and 2015 were included. TO was defined as the percentage of patients who had abdominal aortic aneurysm-repair without intraoperative complications, postoperative surgical complications, reinterventions, prolonged hospital stay endovascular aneurysm repair (EVAR) ≤4 d, open surgical repair (OSR) ≤10 d, readmissions, and postoperative mortality (≤30 d after surgery/at discharge). Case-mix adjusted TO rates were used to compare hospitals and to compare individual hospital results for different procedures.
RESULTS:Five thousand one hundred seventy patients were included, of whom 4039 were treated with EVAR and 1131 with OSR. TO was achieved in 71% of EVAR and 53% of OSR. Important obstacles for achieving TO were a prolonged hospital stay, postoperative complications, and readmissions. Adjusted TO rates varied from 38% to 89% (EVAR) and from 0% to 97% (OSR) between individual hospitals. Hospitals with a high TO for OSR also had a high TO for EVAR; however, a high TO for EVAR did not implicate a high TO for OSR.
CONCLUSIONS:TO generates additional information to evaluate the overall quality of the care of elective aneurysm surgery, which subsequently can be used by hospitals to improve the quality of their care.
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in ...cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models. As an adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection site and reduced metastatic tumor load, which was associated with fewer Th17 cells and increased CD11b+GR1hi myeloid cells. Adoptive transfer of T cells isolated from vaccine-treated tumor-bearing mice inhibited tumor growth in unvaccinated recipients, indicating that the iPSC vaccine promotes an antigen-specific anti-tumor T cell response. Our data suggest an easy, generalizable strategy for multiple types of cancer that could prove highly valuable in clinical immunotherapy.
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•Irradiated iPSCs prevent tumor growth in murine models of breast, lung, and skin cancer•iPSC vaccines target shared antigens between iPSCs and cancer cells•iPSC vaccines promote a humoral and cell-mediated anti-tumor immune profile•As an adjuvant cancer therapy, iPSC vaccination can reactivate the immune system
Wu and colleagues show that cancer immunity against multiple types of cancer can be achieved using an easily generalizable iPSC-based cancer vaccine. This immunity is based on overlapping epitopes between iPSCs and cancer cells and can also be achieved by reactivating the immune system as an adjuvant immunotherapy.
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