Aortic pseudoaneurysm - An unusual presentation

Introduction: The esophagus is a frequent site of foreign body impaction, but esophageal perforation and subsequent aortic pseudoaneurysms, and aorto-esophageal fistulas are very rare but potentially life-threatening complications. We present a case of foreign body ingestion, complicated by erosion into the aorta causing a mycotic aneurysm. Case description: We introduce the case of a 60 year-old male with abdominal pain, nausea, fatigue and fevers. Blood cultures grew out gram-positive cocci. A CT scan revealed a distal thoracic aortic saccular aneurysm, with a 2.8 cm linear metallic body penetrating the inferior border of the aneurysm, and intraluminal thrombus formation. CT of the abdomen revealed portal vein thrombosis, splenic and hepatic abscesses. An Esophagogastroduodenoscopy was unremarkable. The patient was started on the appropriate antibiotic therapy. He was then taken to the operating room for an open thoracoabdominal aortic aneurysm repair with an interposition cryopreserved graft, with an intercostal muscle flap. A metal bristle was removed. He had an uneventful postoperative course and was discharged home on post-operative day 17. Follow-up CTA showed resolution of the infection and satisfactory repair. Post-operative esophagram showed no esophageal injury. Conclusion: We describe a case of a bristle from a metallic barbeque brush that was ingested. This penetrated the esophagus causing a mycotic aneurysm with septic embolization to the spleen and liver. Our successful treatment approach involved open aortic repair with an interposition cryopreserved graft, and an intercostal muscle flap.https://scholarlycommons.henryford.com/merf2020caserpt/1100/thumbnail.jp

Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip/Palate

Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact. Since tooth agenesis is commonly found in individuals with cleft lip/palate (CL/P), we used four large cohorts to evaluate if IRF6 and TGFA interaction contributes to CL/P. Markers within and flanking IRF6 and TGFA genes were tested using Taqman or SYBR green chemistries for case-control analyses in 1,000 Brazilian individuals. We looked for evidence of gene-gene interaction between IRF6 and TGFA by testing if markers associated with CL/P were overtransmitted together in the case-control Brazilian dataset and in the additional family datasets. Genotypes for an additional 142 case-parent trios from South America drawn from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), 154 cases from Latvia, and 8,717 individuals from several cohorts were available for replication of tests for interaction. Tgfa and Irf6 expression at critical stages during palatogenesis was analyzed in wild type and Irf6 knockout mice. Markers in and near IRF6 and TGFA were associated with CL/P in the Brazilian cohort (p<10-6). IRF6 was also associated with cleft palate (CP) with impaction of permanent teeth (p<10-6). Statistical evidence of interaction between IRF6 and TGFA was found in all data sets (p = 0.013 for Brazilians; p = 0.046 for ECLAMC; p = 10-6 for Latvians, and p = 0.003 for the 8,717 individuals). Tgfa was not expressed in the palatal tissues of Irf6 knockout mice. IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies. Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans. © 2012 Letra et al

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction&gt;0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Challenges Of Cave Management In A Developing Country: A Case Study Of Grotte Marie-Jeanne, Departemente Sud, Haiti

As with many developing countries,Haiti has environmental, economic and cultural challenges that complicate natural resource management. Karst landscapes dominate Haiti and caves are abundant as recent cave and karst inventory data indicate. Though the caves and karst are subject to environmental challenges they also provide the potential for the development of tourism that would improve local economic conditions. There are 500 documented caves in Haiti of which, five are show caves. Of those, only one, Grotte Marie-Jeanne, located in Port-ấ -Piment in Departement Sud, has a structured cave management plan that addresses identification of cave resources, visitor access, interpretive guidelines, cave conservation and preservation. Despite economic and political challenges, this recently implemented community-based initiative toward cave development and management is showing success in promoting sustainable ecotourism to the area and providing the basis for the study, conservation and protection of caves and karst throughout Haiti

Mycotic Aneurysm After Metallic Foreign Body Ingestion

Objective: The esophagus is a frequent foreign body impaction site. We present a case of foreign body ingestion complicated by erosion into the aorta, causing a mycotic aneurysm. Methods: We introduce the case of a 60-year-old man with abdominal pain, nausea, fatigue, and fevers. Blood cultures grew out gram-positive cocci. A computed tomography (CT) scan revealed a distal thoracic aortic saccular aneurysm, with a 2.8-cm linear metallic body penetrating the inferior border of the aneurysm, and intraluminal thrombus formation (Fig, A). CT of the abdomen revealed portal vein thrombosis and splenic and hepatic abscesses. Esophagogastroduodenoscopy was unremarkable. Results: The patient was started on the appropriate antibiotic therapy. He was then taken to the operating room for an open thoracoabdominal aortic aneurysm repair with an interposition cryopreserved graft, with an intercostal muscle flap (Fig, B). A metal bristle was removed (Fig, C). He had an uneventful postoperative course and was discharged home on postoperative day 17. Follow-up CT angiography showed resolution of the infection and satisfactory repair (Fig, D). Postoperative esophagram showed no esophageal injury. Conclusions: We describe a case of a bristle from a metallic barbecue brush that was ingested. This penetrated the esophagus, causing a mycotic aneurysm with septic embolization to the spleen and liver. Our successful treatment approach involved open aortic repair with an interposition cryopreserved graft and an intercostal muscle flap

CESSDA SaW D3.6: Final integrated audit report

This is a follow-up of D3.2. The focus is on identifying what development steps can be proposed to tackle the obstacles in the way of achieving the widened and strengthened CESSDA ERIC. The maturity of data archive service (DAS) in most European countries was audited. The analysis contains elements of the wider data sharing ecosystem

Robot-Assisted Minimally Invasive Ivor Lewis Esophagectomy With Real-Time Perfusion Assessment

BACKGROUND: Surgical resection is viewed as the most effective way to ensure both locoregional control and long-term survival in esophageal cancer. Although minimally invasive esophagectomy has been widely accepted as an alternative to open surgery, the role of robotic assistance has yet to be elucidated. We report our institutional experience with robotic-assisted Ivor Lewis esophagectomy using real-time perfusion assessment and demonstrate this as a safe and technically feasible alternative to traditional open Ivor Lewis esophagectomy. METHODS: A retrospective chart review of all patients undergoing robotic-assisted Ivor Lewis esophagectomy at a single institution from 2011 to 2014 was performed. Operative and postoperative outcomes were recorded. RESULTS: Fifty-four patients underwent robotic-assisted Ivor Lewis esophagectomy during the study period. Indication for surgery was cancer in 49 patients, 38 of whom underwent neoadjuvant chemoradiation therapy. The average operative time was 6 hours 2 minutes, and the average blood loss was 74 mL. There was 1 postoperative mortality (1.9%). Three (5.5%) patients experienced an anastomotic leak. The average number of lymph nodes harvested in cancer patients was 16.2 (range, 3 to 35). The average length of stay was 12.9 days. CONCLUSIONS: Our study demonstrates that robotic-assisted Ivor Lewis esophagectomy using real-time perfusion assessment is a safe and technically feasible alternative to traditional open Ivor Lewis esophagectomy. It allows for R0 resection with adequate lymph node harvesting and a short hospital stay