Usa1 functions as a scaffold of the HRD-ubiquitin ligase.

Protein quality control in the endoplasmic reticulum is of central importance for cellular homeostasis in eukaryotes. Crucial for this process is the HRD-ubiquitin ligase (HMG-CoA reductase degradation), which singles out terminally misfolded proteins and routes them for degradation to cytoplasmic 26S-proteasomes. Certain functions of this enzyme complex are allocated to defined subunits. However, it remains unclear how these components act in a concerted manner. Here, we show that Usa1 functions as a major scaffold protein of the HRD-ligase. For the turnover of soluble substrates, Der1 binding to the C terminus of Usa1 is required. The N terminus of Usa1 associates with Hrd1 and thus bridges Der1 to Hrd1. Strikingly, the Usa1 N terminus also induces oligomerization of the HRD complex, which is an exclusive prerequisite for the degradation of membrane proteins. Our data demonstrate that scaffold proteins are required to adapt ubiquitin ligase activities toward different classes of substrates.

Five-year results for endovascular repair of acute complicated type B aortic dissection.

INTRODUCTION: Despite a current lack of U.S. Food and Drug Administration approval for the indication, thoracic endovascular aortic repair (TEVAR) has replaced open surgical management for acute complicated type B aortic dissection due to promising short- and midterm data. However, long-term results, with a view toward durability and need for secondary procedures, are limited. As such, the objective of the present study is to report long-term outcomes of TEVAR for acute (≤ 2 weeks from symptom onset) complicated type B dissection. METHODS: Between July 2005 and September 2012, 50 consecutive patients underwent TEVAR for management of acute complicated type B dissection at a single referral institution. Patient records were retrospectively reviewed from a prospectively maintained clinical database. RESULTS: Indications for intervention included rupture in 10 (20%), malperfusion in 24 (48%), and/or refractory pain/impending rupture in 17 (34%). One patient (2%) had both rupture and malperfusion indications. Ten (20%) patients required one or more adjunctive procedures, in addition to TEVAR, to treat malperfusion syndromes. In-hospital and 30-day rates of death were both 0%; 30-day/in-hospital rates of stroke, permanent paraplegia/paraparesis, and new-onset dialysis were 2% (n = 1), 2% (n = 1), and 4% (n = 2), respectively. Median follow-up was 33.8 months [interquartile range, 12.3-56.6 months]. Overall survival at 5 and 7 years was 84%, with no deaths attributable to aortic pathology. Thirteen (26%) patients required a total of 17 reinterventions over the study period for type I endoleak (n = 5), metachronous aortic pathology (n = 5), persistent false lumen pressurization via distal fenestrations (n = 4), type II endoleak (n = 2), or retrograde acute type A aortic dissection (n = 1). Median time to first reintervention was 4.5 months (range, 0 days-40.3 months). Of the 17 total reinterventions, six (35%) were performed using open techniques and 11 (65%) with endovascular or hybrid methods; there was no difference in survival between patients who did or did not require reintervention. CONCLUSIONS: This study confirms the excellent short-term outcomes of TEVAR for acute complicated type B dissection and demonstrates the results to be durable and sustained over long-term follow-up. Although aortic reinterventions were required in one-quarter of patients, no aortic-related deaths were observed. These data support the use of TEVAR for acute complicated type B aortic dissection but also highlight the importance of life-long aortic surveillance by an experienced aortic referral center in order to identify and treat complications of the underlying disease process and treatment, as well as new aortic pathologies, as they arise.

Comparison of attachment site endoleak rates in Dacron versus native aorta landing zones after thoracic endovascular aortic repair.

OBJECTIVE: Type I attachment site endoleaks are the most common cause for reintervention after thoracic endovascular aortic repair (TEVAR) and represent treatment failures. Deployment of endografts in segments of the aorta previously replaced with Dacron grafts may be associated with reduced type I endoleak due to mechanical stability and decreased potential for aortic remodeling. However, no study has rigorously examined endoleak rates in Dacron landing zones vs native aorta. METHODS: A retrospective analysis of a prospectively maintained database was performed to identify all patients undergoing TEVAR at a single referral institution between May 2002 and June 2012. Overall, 319 patients undergoing 345 procedures had at least one follow-up contrast-enhanced computed tomography scan to assess for postoperative type I endoleak. Attachment site landing zones were classified as native aorta, Dacron, or endograft if landed in a previously placed endograft. Patient characteristics and type I endoleak rates were compared among the three groups. RESULTS: Identified were 697 proximal or distal landing zones (native aorta, 599; Dacron, 79; and endograft, 19). Patients with at least one Dacron landing zone had higher rates of hypertension (P < .01), chronic obstructive pulmonary disease (P = .04), and prior aortic surgery (P < .01) and were more likely to have undergone complex hybrid repairs (P < .01). Cumulative type I endoleak rates were equivalent between the three types of landing zone (native aorta, 3.7%; Dacron, 2.5%; endograft, 0%; P = .44). Two type I endoleaks occurred with Dacron landing zones in the first tertile of TEVAR experience and with Dacron landing zone lengths of <2.5 cm. Evaluation of endoleak rates by tertile of experience demonstrated decreased type I endoleak rates in Dacron landing zones between the first and second/third tertiles of experience (13.3% vs 0%, P = .03) after a policy of using >4 to 5 cm (twice the device instructions for use) of Dacron overlap was initiated. CONCLUSIONS: Endograft deployment within long-segment (landing zone length of >4-5 cm) Dacron represents a durable option for aortic repair and was associated with a 0% rate of type I endoleak. In cases of a borderline native aortic landing zone, a hybrid procedure to create an adequate Dacron landing zone may be warranted to decrease the risk of type I endoleak and treatment failure.

Rectourethral fistulas in the cancer survivor.

PURPOSE OF REVIEW: Iatrogenic rectourethral fistulas (RUFs) are a rare but challenging complication that can follow the treatment of prostate cancer. We review the literature regarding the surgical management of RUFs and subsequent outcomes, focusing on a cause-specific approach. RECENT FINDINGS: Iatrogenic RUFs are reported to occur in approximately 1% of patients treated with external-beam radiation therapy, in 1-6% of patients after radical prostatectomy, and in 5-9% following brachytherapy or cryotherapy after prostate cancer. Most of these patients will require surgical treatment at some point. Though there have been multiple surgical procedures described with varying degrees of success, there is no consensus as to the procedure of choice, though authors now agree on the importance of the interposition of healthy tissue in radiation-induced fistulas. SUMMARY: The current literature regarding surgical approaches to the iatrogenic RUF in the prostate cancer patient highlights the importance of a cause-specific and often multidisciplinary approach, as well as the one that is most familiar to the individual surgeon, because there is often little difference in the approaches in terms of recurrence. However, given the high success rate and low complication rate, muscle transposition flap repairs remain an attractive surgical option for fistulas with unfavorable local conditions such as those present after radiation.

Surgical management of complex rectourethral fistulas in irradiated and nonirradiated patients.

BACKGROUND: Rectourethral fistulas are an uncommon, yet devastating occurrence after treatment for prostate cancer or trauma, and their surgical management has historically been nonstandardized. Anecdotally, irradiated rectourethral fistulas portend a worse prognosis. OBJECTIVE: To review outcomes after surgical treatment of rectourethral fistulas in radiated and nonirradiated patients to construct a logical surgical algorithm. DESIGN AND SETTING: A retrospective review was undertaken of all patients presenting to Duke University with the diagnosis of rectourethral fistula from 1996 to 2012. PATIENTS: Thirty-seven patients presented with and were treated for rectourethral fistulas: 21 received radiation, and a rectourethral fistula from trauma or iatrogenic injury developed in 16. MAIN OUTCOME MEASURES: The groups were compared regarding their functional outcomes, including healing, time to healing, continence, and recurrence. RESULTS: There were no significant differences in patient characteristics between groups. Patients who had irradiated rectourethral fistulas had a significantly higher rate of passage of urine through the rectum and wound infections, a higher rate of crystalloid infusion and blood transfusion requirements, and a longer time to ostomy reversal than nonirradiated patients. Patients who had irradiated rectourethral fistulas underwent more complex operative repairs, including gracilis interposition flaps (38%) and pelvic exenterations (19%), whereas nonirradiated patients most commonly underwent a York-Mason repair (50%). There were no statistically significant differences in rectourethral fistula healing or in postoperative and functional outcomes. Only 55% of irradiated patients had their ostomy reversed versus 91% in the nonirradiated group. LIMITATIONS: This study was limited by the small sample size and the retrospective nature of the review. CONCLUSIONS: Repair of rectourethral fistulas caused by radiation has a significantly higher wound infection rate and median time to healing, and lower overall stomal reversal rate than nonradiation-induced rectourethral fistulas. Patients who had irradiated rectourethral fistulas required significantly more complex operations, likely contributing to the higher morbidity, mortality, and lower fistula closure rate. We propose an algorithm for approaching rectourethral fistulas based on etiology.

Structural and biochemical basis of Yos9 protein dimerization and possible contribution to self-association of 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation ubiquitin-ligase complex.

In yeast, the membrane-bound HMG-CoA reductase degradation (HRD) ubiquitin-ligase complex is a key player of the ER-associated protein degradation pathway that targets misfolded proteins for proteolysis. Yos9, a component of the luminal submodule of the ligase, scans proteins for specific oligosaccharide modifications, which constitute a critical determinant of the degradation signal. Here, we report the crystal structure of the Yos9 domain that was previously suggested to confer binding to Hrd3, another component of the HRD complex. We observe an αß-roll domain architecture and a dimeric assembly which are confirmed by analytical ultracentrifugation of both the crystallized domain and full-length Yos9. Our binding studies indicate that, instead of this domain, the N-terminal part of Yos9 including the mannose 6-phosphate receptor homology domain mediates the association with Hrd3 in vitro. Our results support the model of a dimeric state of the HRD complex and provide first-time evidence of self-association on its luminal side.

Intrathoracic subclavian artery aneurysm repair in the thoracic endovascular aortic repair era.

OBJECTIVE: Intrathoracic subclavian artery aneurysms (SAAs) are rare aneurysms that often occur in association with congenital aortic arch anomalies and/or concomitant thoracic aortic pathology. The advent of thoracic endovascular aortic repair (TEVAR) methods may complement or replace conventional open SAA repair. Herein, we describe our experience with SAA repair in the TEVAR era. METHODS: A retrospective review was performed of all intrathoracic SAAs repaired at a single institution since United States Food and Drug Administration approval of TEVAR in 2005. RESULTS: Nineteen patients underwent 20 operations to repair 22 (13 native, nine aberrant) SAAs with an intrathoracic component. Mean SAA diameter was 3.1 cm (range, 1.6-6.0 cm). Mean patient age was 57 years (range, 24-80 years). Twenty-one percent (n = 4) of patients had a connective tissue disorder (two Loeys-Dietz, two Marfan). Thirty-six percent (n = 8) of SAAs were repaired by open techniques and 64% (n = 14) via a TEVAR-based approach. All TEVAR cases required proximal landing zone in the aortic arch (zone 0-2), and revascularization of at least one arch vessel was required in 83% (10/12) of patients. Concomitant repair of associated aortic pathology was performed in 50% (n = 10) of operations. Thirty-day/in-hospital rates of death, stroke, and permanent paraplegia/paraparesis were 5% (n = 1), 5% (n = 1), and 0%, respectively. Over mean (standard deviation) follow-up of 24 (21) months, 16% (n = 3) of patients required reintervention for subclavian artery bypass graft revision (n = 2) or type II endoleak (n = 1). CONCLUSIONS: This is the largest single-institution series to date of TEVAR for SAA repair. Modern endovascular techniques expand SAA repair options with excellent results. The majority of SAAs and nearly all aberrant SAAs (Kommerell's diverticulum) can now be repaired using a TEVAR-based approach without the need for sternotomy or thoracotomy.

Results with an algorithmic approach to hybrid repair of the aortic arch.

OBJECTIVE: Hybrid repair of the transverse aortic arch may allow for aortic arch repair with reduced morbidity in patients who are suboptimal candidates for conventional open surgery. We present our results with an algorithmic approach to hybrid arch repair, based on the extent of aortic disease and patient comorbidities. METHODS: Between August 2005 and January 2012, 87 patients underwent hybrid arch repair by three principal procedures: zone 1 endograft coverage with extra-anatomic left carotid revascularization (zone 1; n = 19), zone 0 endograft coverage with aortic arch debranching (zone 0; n = 48), or total arch replacement with staged stented elephant trunk completion (stented elephant trunk; n = 20). RESULTS: The mean patient age was 64 years, and the mean expected in-hospital mortality rate was 16.3% as calculated by the EuroSCORE II. Of operations, 22% (n = 19) were nonelective. Sternotomy, cardiopulmonary bypass, and deep hypothermic circulatory arrest were required in 78% (n = 68), 45% (n = 39), and 31% (n = 27) of patients to allow for total arch replacement, arch debranching, or other concomitant cardiac procedures, including ascending with or without hemiarch replacement in 17% (n = 8) of patients undergoing zone 0 repair. All stented elephant trunk procedures (n = 20) and 19% (n = 9) of zone 0 procedures were staged, with 41% (n = 12) of patients undergoing staged repair during a single hospitalization. The 30-day/in-hospital rates of stroke and permanent paraplegia or paraparesis were 4.6% (n = 4) and 1.2% (n = 1). Of 27 patients with native ascending aorta zone 0 proximal landing zone, three (11.1%) experienced retrograde type A dissection after endograft placement. The overall in-hospital mortality rate was 5.7% (n = 5); however, 30-day/in-hospital mortality increased to 14.9% (n = 13) owing to eight 30-day out-of-hospital deaths. Native ascending aorta zone 0 endograft placement was found to be the only univariate predictor of 30-day in-hospital mortality (odds ratio, 4.63; 95% confidence interval, 1.35-15.89; P = .02). Over a mean follow-up period of 28.5 ± 22.2 months, 13% (n = 11) of patients required reintervention for type 1A (n = 4), type 2 (n = 6), or type 3 (n = 1) endoleak. Kaplan-Meier estimates of survival at 1 year, 3 years, and 5 years were 73%, 60%, and 51%. CONCLUSIONS: Hybrid aortic arch repair can be tailored to patient anatomy and comorbid status to allow complete repair of aortic pathology, frequently in a single stage, with acceptable outcomes. However, endograft placement in the native ascending aorta is associated with high rates of retrograde type A dissection and 30-day/in-hospital mortality and should be approached with caution.

Cell of origin of lung cancer.

Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s) of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell of origin, and cancer stem cells has been hampered by the heterogeneity of the disease, the lack of good in vivo transplantation models to assess stem cell behavior, and an overall incomplete understanding of the epithelial stem cell hierarchy. As such, a systematic computerized literature search of the MEDLINE database was used to identify articles discussing current knowledge about normal lung and lung cancer stem cells or progenitor cells. In this review, we discuss what is currently known about the role of cancer-initiating cells and normal stem cells in the development of lung tumors.

Fibrinogen and FXIII dose response effects on albumin-induced coagulopathy.

OBJECTIVES: Natural colloid albumin induces a lesser degree of dilutional coagulopathy than synthetic colloids. Fibrinogen concentrate has emerged as a promising strategy to treat coagulopathy, and factor XIII (FXIII) works synergistically with fibrinogen to correct coagulopathy following haemodilution with crystalloids. Our objectives were to examine the ability of fibrinogen and FXIII concentrates to reverse albumin-induced dilutional coagulopathy. METHODS: High and low concentrations of both fibrinogen and FXIII were used to reverse coagulopathy induced by 1:1 dilution in vitro with 5% albumin of blood samples from healthy volunteers, monitored by rotational thromboelastometry (ROTEM). RESULTS: Haemodilution with albumin significantly attenuated EXTEM maximum clot firmness (MCF), alpha angle (AA), clotting time (CT) and clot formation time (CFT), and FIBTEM MCF (p < 0.001). Following haemodilution, both doses of fibrinogen significantly corrected all ROTEM parameters (p ≤ 0.02), except the lower dose did not correct AA. Compared to the lower dose, the higher dose of fibrinogen significantly improved FIBTEM MCF and EXTEM MCF, AA and CFT (p < 0.001). The lower dose of FXIII did not significantly correct any of the ROTEM parameters, and the high dose only improved EXTEM CT (p = 0.004). All combinations of high/low concentrations of fibrinogen/FXIII significantly improved all ROTEM parameters examined (p ≤ 0.001). Fibrinogen concentration generally had a greater effect on each parameter than did FXIII concentration; the best correction of ROTEM parameters was achieved with high-dose fibrinogen concentrate and either low- or high-dose FXIII. CONCLUSIONS: Fibrinogen concentrate successfully corrected initiation, propagation and clot firmness deficits induced by haemodilution with albumin, and FXIII synergistically improved fibrin-based clot strength.

Albumin-induced coagulopathy is less severe and more effectively reversed with fibrinogen concentrate than is synthetic colloid-induced coagulopathy.

BACKGROUND: Synthetic colloids cause dilutional coagulopathy. The aims of our study were to determine whether the natural colloid albumin induces a lesser degree of coagulopathy compared to synthetic colloids, and the comparative effectiveness of fibrinogen concentrate to reverse coagulopathy following dilution with these solutions. METHODS: Coagulation was assessed with rotational thrombelastometry after stimulation with tissue factor (EXTEM) and in the presence of a platelet inhibitor (FIBTEM). With EXTEM, clotting time (CT), clot formation time CFT), alpha angle (AA) and maximum clot firmness (MCF) were recorded. With FIBTEM, only MCF was recorded. These parameters were assessed ex vivo in blood from 10 healthy volunteers; diluted 1:1 with either saline, Ringer's acetate, buffered/unbuffered hydroxyethyl starch, buffered/unbuffered dextran (synthetic colloids) or 5% albumin. Samples were analyzed before/after addition of fibrinogen concentrate. RESULTS: FIBTEM MCF decreased significantly upon dilution (> 50% reduced) with all colloid solutions (p ≤ 0.02), although a significantly greater coagulopathic effect was seen for samples diluted with synthetic colloids versus albumin (p ≤ 0.001). A significant reduction in the platelet component of clot strength (EXTEM MCF - FIBTEM MCF) was seen for samples diluted with synthetic colloids (p < 0.001) but not albumin (p = 0.10). Following addition of fibrinogen, FIBTEM MCF, EXTEM MCF and AA were significantly higher, and CFT was significantly shorter in samples diluted with albumin versus those treated with synthetic colloids (p ≤ 0.001). CONCLUSION: Hemodilution using albumin induced a lesser degree of coagulopathy compared with the synthetic colloids. In addition, albumin-induced coagulopathy was more effectively reversed following addition of fibrinogen concentrate compared with coagulopathy induced by synthetic colloids.

Staged total abdominal debranching and thoracic endovascular aortic repair for thoracoabdominal aneurysm.

OBJECTIVE: Thoracoabdominal aortic aneurysms (TAAAs) occur most commonly in elderly individuals, who are often suboptimal candidates for open repair because of significant comorbidities. The availability of a hybrid option, including open visceral debranching with endovascular aneurysm exclusion, may have advantages in these patients who are at high-risk for conventional repair. This report details the evolution of our technique and results with complete visceral debranching and endovascular aneurysm exclusion for TAAA repair in high-risk patients. METHODS: Between March 2005 and June 2011, 47 patients (51% women) underwent extra-anatomic debranching of all visceral vessels, followed by aneurysm exclusion by endovascular means at a single institution. A median of four visceral vessels were bypassed. The debranching procedure was initially performed through a partial right medial visceral rotation approach, leaving the left kidney posterior in the first 22 patients, and in the last 25 by a direct anterior approach to the visceral vessels. The debranching and endovascular portions of the procedure were performed in a single operation in the initial 33 patients and as a staged procedure during a single hospital stay in the most recent 14. RESULTS: Median patient age was 71.0 ± 9.8 years. All had significant comorbidity and were considered suboptimal candidates for conventional repair: 55% had undergone previous aortic surgery, 40% were American Society of Anesthesiologists (ASA) class 4, and baseline serum creatinine was 1.5 ± 1.3 mg/dL. The 30-day/in-hospital rates of death, stroke, and permanent paraparesis/plegia were 8.5%, 0%, and 4.3%, respectively, but 0% in the most recent 14 patients undergoing staged repair. These patients had significantly shorter combined operative times (314 vs 373 minutes), decreased intraoperative red blood cell transfusions (350 vs 1400 mL), and were more likely to be extubated in the operating room (50% vs 12%) compared with patients undergoing simultaneous repair. Over a median follow-up of 19.3 ± 18.5 months, visceral graft patency was 97%; all occluded limbs were to renal vessels and clinically silent. There have been no type I or III endoleaks or reinterventions. Kaplan-Meier overall survival is 70.7% at 2 years and 57.9% at 5 years. CONCLUSIONS: Hybrid TAAA repair through complete visceral debranching and endovascular aneurysm exclusion is a good option for elderly high-risk patients less suited to conventional repair in centers with the requisite surgical expertise with visceral revascularization. A staged approach to debranching and endovascular aneurysm exclusion during a single hospitalization appears to yield optimal results.

Use of a serious game simulation to build early childhood staff capacity for reducing unintentional childhood injuries.

INTRODUCTION: Unintentional home injuries are common and costly, with over 1.6 million occurring among U.S. children ages 0-4 in 2018. Home visitors and other early childhood professionals can provide valuable prevention education and intervention to reduce unintentional injury risk for children. This proof-of-concept study aimed to test the feasibility of the first phase of Home Safety Hero, a software-based serious game simulation that trains users in identification of home safety risks, as a capacity building tool for early childhood professionals. METHODS: The game simulation's potential for knowledge promotion and engagement in a sample of home visitors was explored based on play of the first phase. Repeated measures ANOVAs were used to assess learning via reaction time, and engagement was measured via the User Engagement Scale (UES). RESULTS: Reaction time (i.e., average time to identify hazards) improved from the first to last levels in both single and mixed category levels in this trial. Participant indicated agreement with four subscales of engagement measured by the UES, and neutral to agree on a fifth subscale, focused attention. CONCLUSIONS: We propose that this game simulation can meet the unique training needs of early childhood professionals while promoting home safety knowledge that can improve prevention work with families. Participant feedback was largely positive, and results suggest that the game simulation is engaging and contributes to knowledge. PRACTICAL APPLICATIONS: The Home Safety Hero serious game simulation is a flexible training option that appeared to be feasible for reducing time to hazard identification among home visitors in this proof-of-concept study. The design of the game simulation has utility in meeting the specialized training needs of early childhood professionals and potential to build their capacity to provide direct intervention around home safety, reducing risk for unintentional injury among children.

Conflict of interest issues pertinent to Veterans Affairs Medical Centers.

Conflicts of interest exist when an arrangement potentially exerts inappropriate influence on decision making or professional judgment, or is perceived to do so, and can thus damage the public trust and undermine the integrity of those decisions. Concerns regarding financial conflicts of interest in the medical arena have reached their height as of late, given that physicians now function in a milieu of complex and delicate relationships with pharmaceutical, biotechnology, and medical device industries. Even when such relationships do not correlate with actual compromise of judgment or patient care, it threatens the credibility of both the health care professional and the institution because of the social perception of the effect of these relationships. Although most institutions in the Western world set forth a code of ethics and conflict-of-interest policies to be followed under threat of termination, the Veterans Health Administration (VHA) presents itself as a unique environment in which conflicts of interest are subject to governmental laws, violation of which may not only result in employment-related discipline, but may be sanctioned by civil and criminal penalties. Moreover, these provisions are developed by a national authoritative organization rather than being institution-specific guidelines. Given that many academic physicians working within the VHA may also have a component of their practice in a University setting, it becomes important to understand the differences in policy between these contexts so as not to threaten the public trust in the veracity of decisions made and, therefore, maintain the integrity of the relationship between physician and patient. This article will review aspects of conflict-of-interest policies in the realm of research, financial relationships, foreign travel, and vendor contracting that are particular to the VHA and make it a unique environment to function in as a physician and scientist.

Isolation protocol for a COVID-2019 patient requiring emergent surgical intervention: case presentation.

BACKGROUND: The concerns of the highly contagious and morbid nature of Coronavirus Disease-2019 (COVID-2019) have prompted healthcare workers to implement strict droplet and contact isolation precautions. Unfortunately, some patients who may be or presumptively or confirmed as infected with COVID-2019 may also require emergent surgical procedures. As such, given the high-risk for exposure of many healthcare workers involved the complex requirements for appropriate isolation must be adhered to. CASE PRESENTATION: We present our experience with a 77-year-old who required emergency cardiac surgery for a presumed acute aortic syndrome in the setting of a presumed, and eventually confirmed, COVID-2019 infection. We outline the necessary steps to maintain strict isolation precautions to limit potential exposure to the surgical Team. CONCLUSIONS: We hereby provide our algorithm for emergent surgical procedures in critically-ill patients with presumptive or confirmed infection with COVID-2019. The insights from this case report can potentially be templated to other facilities in order to uphold high standards of infection prevention and patient safety in surgery during the current COVID-19 pandemic.

Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report.

BACKGROUND: The value of extracorporeal membrane oxygenation (ECMO) for patients suffering from novel coronavirus disease 2019 (COVID-19) as a rescue therapy for respiratory failure remains controversial and associated with high mortality rates of 50 to 82% in early reports from Wuhan, China. We hypothesized that patient outcomes would be improved at our tertiary cardiothoracic surgery referral center with a protocolized team-approach for ECMO treatment of patients with severe COVID-19 disease. CASE PRESENTATION: A 51-year-old healthy female developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) bilateral pneumonia while vacationing in Colorado with her family. She was transferred to our facility for a higher level of care. Her respiratory status continued to deteriorate despite maximized critical care, including prone positioning ventilation and nitric oxide inhalation therapy. Veno-venous ECMO was initiated on hospital day 7 in conjunction with a 10-day course of compassionate use antiviral treatment with remdesivir. The patient's condition improved significantly and she was decannulated from ECMO on hospital day 17 (ECMO day 11). She was successfully extubated and eventually discharged to rehabilitation on hospital day 28. CONCLUSION: This case report demonstrates a positive outcome in a young patient with COVID-19 treated by the judicious application of ECMO in conjunction with compassionate use antiviral treatment (remdesivir). Future prospective multi-center studies are needed to validate these findings in a larger cohort of patients.

Complete pulmonary recovery after COVID-19 infection requiring extracorporeal membrane oxygenation: A case report.

Severe pulmonary complications associated with COVID-19 infections are a substantial source of morbidity and/or mortality. Extracorporeal membrane oxygenation (ECMO) has been shown to be a potentially useful therapy in the management of severe COVID-19 infection as a means to facilitate pulmonary recovery. Despite growing evidence to demonstrate the utility of ECMO for COVID-19 respiratory failure, little is known regarding the posthospital discharge recovery and functional status of these patients. Furthermore, concerns regarding potential long-term complications, but data are lacking. We illustrate a case of a previously healthy male, who was supported on ECMO for severe COVID-19 who demonstrated what appears to be a complete subjective and objective pulmonary recovery within a short time postdischarge. Our case provides some optimisms that critically-ill COVID-19 patients might recover completely and be able to return to functional lives.

Management of No-Reflow Phenomenon in the Catheterization Laboratory.

At the conclusion of a primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, and after the cardiologist makes certain that there is no residual stenosis following stenting, assessment of coronary flow becomes the top priority. The presence of no-reflow is a serious prognostic sign. No-reflow can result in poor healing of the infarct and adverse left ventricular remodeling, increasing the risk for major adverse cardiac events, including congestive heart failure and death. To achieve normal flow, features associated with a high incidence of no-reflow must be anticipated, and measures must be undertaken to prevent its occurrence. In this review, the authors discuss various preventive strategies for no-reflow as well as pharmacological and nonpharmacological interventions that improve coronary blood flow, such as intracoronary adenosine and nitroprusside. Nonpharmacological therapies, such as induced hypothermia, were successful in animal studies, but their effectiveness in reducing no-reflow in humans remains to be determined.

Use of human fibrinogen concentrate during proximal aortic reconstruction with deep hypothermic circulatory arrest.

OBJECTIVE: Human fibrinogen concentrate (HFC) is approved by the Food and Drug Administration for use at 70 mg/kg to treat congenital afibrinogenemia. We sought to determine whether this dose of HFC increases fibrinogen levels in the setting of high-risk bleeding associated with aortic reconstruction and deep hypothermic circulatory arrest (DHCA). METHODS: This was a prospective, pilot, off-label study in which 22 patients undergoing elective proximal aortic reconstruction with DHCA were administered 70 mg/kg HFC upon separation from cardiopulmonary bypass (CPB). Fibrinogen levels were measured at baseline, just before, and 10 minutes after HFC administration, on skin closure, and the day after surgery. The primary study outcome was the difference in fibrinogen level immediately after separation from CPB, when HFC was administered, and the fibrinogen level 10 minutes following HFC administration. Additionally, postoperative thromboembolic events were assessed as a safety analysis. RESULTS: The mean baseline fibrinogen level was 317 ± 49 mg/dL and fell to 235 ± 39 mg/dL just before separation from CPB. After HFC administration, the fibrinogen level rose to 331 ± 41 mg/dL (P < .001) and averaged 372 ± 45 mg/dL the next day. No postoperative thromboembolic complications occurred. CONCLUSIONS: Administration of 70 mg/kg HFC upon separation from CPB raises fibrinogen levels by approximately 100 mg/dL without an apparent increase in thrombotic complications during proximal aortic reconstruction with DHCA. Further prospective study in a larger cohort of patients will be needed to definitively determine the safety and evaluate the efficacy of HFC as a hemostatic adjunct during these procedures.