Eight-year outcomes of aortic valve replacement with the Carpentier-Edwards PERIMOUNT Magna Ease valve.

INTRODUCTION: The Carpentier-Edwards PERIMOUNT Magna Ease valve is a third-generation bioprosthesis for aortic valve replacement (AVR). This is a postapproval study reporting on its 8-year outcomes. METHODS: Adults undergoing AVR with the Magna Ease valve between October 2007 and December 2012 were enrolled for this prospective, nonrandomized, single-arm, and multicenter study. Assessments occurred preoperatively, at hospital discharge, 6 months, 1 year, and annually thereafter for up to 8 years. Outcomes included safety endpoints, hemodynamic performance, and New York Heart Association (NYHA) functional class. RESULTS: Of the 258 study patients, 67.5% were in NYHA Class I or II, and 32.5% were in NYHA Class III or IV at baseline. Concomitant procedures were performed in 44.2%. Total follow-up was 1597.6 patient-years, and median follow-up was 7 years (interquartile range: 5.5-8.0 years). Eight years following AVR, the functional class remained improved from baseline with 93.9% in NYHA Class I/II and 6.1% in NYHA Class III; 38 deaths had occurred, 8 of which were valve related; freedom from all-cause mortality was 80.7% (95% confidence intervals: 74.9, 86.4); freedom from valve-related mortality was 95.8% (92.8, 98.8); freedom from reintervention, explant, major bleeding events, and structural valve deterioration was 89.8% (85.1, 94.6), 94.8% (91.7, 97.9), 85.1% (80.0, 90.1), and 90.1% (84.7, 95.4), respectively; effective orifice area was 1.5 ± 0.5 cm2 , the mean gradient was 14.8 ± 8.3 mmHg, and 88.6% of patients had no or trivial aortic regurgitation. CONCLUSIONS: This study demonstrated satisfactory safety and sustained hemodynamic and functional improvements at 8 years following AVR with the Magna Ease valve.

Mediastinal Masses, Anesthetic Interventions, and Airway Compression in Adults: A Prospective Observational Study.

BACKGROUND: Central airway occlusion is a feared complication of general anesthesia in patients with mediastinal masses. Maintenance of spontaneous ventilation and avoiding neuromuscular blockade are recommended to reduce this risk. Physiologic arguments supporting these recommendations are controversial and direct evidence is lacking. The authors hypothesized that, in adult patients with moderate to severe mediastinal mass-mediated tracheobronchial compression, anesthetic interventions including positive pressure ventilation and neuromuscular blockade could be instituted without compromising central airway patency. METHODS: Seventeen adult patients with large mediastinal masses requiring general anesthesia underwent awake intubation followed by continuous video bronchoscopy recordings of the compromised portion of the airway during staged induction. Assessments of changes in anterior-posterior airway diameter relative to baseline (awake, spontaneous ventilation) were performed using the following patency scores: unchanged = 0; 25 to 50% larger = +1; more than 50% larger = +2; 25 to 50% smaller = -1; more than 50% smaller = -2. Assessments were made by seven experienced bronchoscopists in side-by-side blinded and scrambled comparisons between (1) baseline awake, spontaneous breathing; (2) anesthetized with spontaneous ventilation; (3) anesthetized with positive pressure ventilation; and (4) anesthetized with positive pressure ventilation and neuromuscular blockade. Tidal volumes, respiratory rate, and inspiratory/expiratory ratio were similar between phases. RESULTS: No significant change from baseline was observed in the mean airway patency scores after the induction of general anesthesia (0 [95% CI, 0 to 0]; P = 0.953). The mean airway patency score increased with the addition of positive pressure ventilation (0 [95% CI, 0 to 1]; P = 0.024) and neuromuscular blockade (1 [95% CI, 0 to 1]; P < 0.001). No patient suffered airway collapse or difficult ventilation during any anesthetic phase. CONCLUSIONS: These observations suggest a need to reassess prevailing assumptions regarding positive pressure ventilation and/or paralysis and mediastinal mass-mediated airway collapse, but do not prove that conventional (nonstaged) inductions are safe for such patients.

Enhanced Recovery After Cardiac Surgery: A Propensity-Matched Analysis.

Enhanced Recovery After Surgery (ERAS) pathways have improved clinical outcomes, cost-effectiveness, and patient satisfaction across multiple non-cardiac surgical specialties. Since the adaptation of ERAS in cardiac surgery is rapidly increasing yet still evolving, herein, we demonstrate early results of our implementation of ERAS cardiac guidelines. We retrospectively reviewed all patients who were managed with our institutional ERAS Cardiac Surgery guidelines between 5/2018 and 6/2019(N = 102). Postoperative primary outcomes (total ventilation times(hours), intensive-care unit(ICU) stay, and postoperative hospital length of stay (LOS)) were compared to 1:1 propensity matched controls from the pre ERAS era between January 2017 and March 2019. A total of 76 propensity-matched pairs were identified. Compared to the matched controls, ERAS patients had significantly shorter median ventilation times(3.5 vs. 5.3 hours, p = .01), ICU stays(median 28 vs 48 hours, p=.005) and postoperative hospital LOS (median 5 vs. 6 days, p = .03). There were no operative mortalities and no significant differences in 30-day readmission rates. There were also no significant differences in post-operative stroke, acute kidney injury, atrial fibrillation, and reoperation rates for bleeding. Two-year survival was also not statistically different between the two cohorts (p = .22). Our initial experience with implementation of ERAS protocols in cardiac surgery appear to demonstrate that these protocols are associated with shorter ventilation times, ICU stay, and hospital LOS without compromising patient outcomes. While these results are promising yet preliminary, further studies are warranted to demonstrate whether ERAS algorithms in cardiac surgery can consistently expedite postoperative recovery and improve outcomes.

Posttraumatic Symptoms, Quality of Life, and Survival among Lung Cancer Patients.

PURPOSE: This longitudinal study characterized psychological adjustment in a sample of lung cancer patients by examining the occurrence of posttraumatic stress and growth and their relationships with mental and physical health quality of life and survival over time. METHODS: Two waves of consecutive cohort samples, totaling 115 participants diagnosed with lung cancer, were identified from outpatient oncology clinics. Of these, 93 consented and completed the first of three assessments, and 57 completed the study. Prevalence of posttraumatic stress symptoms (PTSD Checklist) and posttraumatic growth (Posttraumatic Growth Inventory) were assessed and used to predict physical and mental health components of quality of life (Short Form 36) and survival. RESULTS: Patients reported both negative and positive psychological sequelae, with prevalence of estimated PTSD ranging from 5-16% at each assessment as determined by symptom and cut-off methods. Posttraumatic stress and growth were positively related, but were differentially associated with outcomes. More posttraumatic stress predicted lower mental health quality of life, whereas more posttraumatic growth predicted better physical health quality of life and longer survival. These relationships persisted after accounting for disease variables and attrition due to death or illness. CONCLUSIONS: These findings highlight the importance of using longitudinal designs to identify relationships between stress and resilience factors in predicting outcomes.

GM-CSF Enhances Macrophage Glycolytic Activity In Vitro and Improves Detection of Inflammation In Vivo.

UNLABELLED: (18)F-FDG accumulates in glycolytically active tissues and is known to concentrate in tissues that are rich in activated macrophages. In this study, we tested the hypotheses that human granulocyte-macrophage colony-stimulating factor (GM-CSF), a clinically used cytokine, increases macrophage glycolysis and deoxyglucose uptake in vitro and acutely enhances (18)F-FDG uptake within inflamed tissues such as atherosclerotic plaques in vivo. METHODS: In vitro experiments were conducted on human macrophages whereby inflammatory activation and uptake of radiolabeled 2-deoxyglucose was assessed before and after GM-CSF exposure. In vivo studies were performed on mice and New Zealand White rabbits to assess the effect of GM-CSF on (18)F-FDG uptake in normal versus inflamed arteries, using PET. RESULTS: Incubation of human macrophages with GM-CSF resulted in increased glycolysis and increased 2-deoxyglucose uptake (P < 0.05). This effect was attenuated by neutralizing antibodies against tumor necrosis factor-α or after silencing or inhibition of 6-phosphofructo-2-kinase. In vivo, in mice and in rabbits, intravenous GM-CSF administration resulted in a 70% and 73% increase (P < 0.01 for both), respectively, in arterial (18)F-FDG uptake in atherosclerotic animals but not in nonatherosclerotic controls. Histopathologic analysis demonstrated a significant correlation between in vivo (18)F-FDG uptake and macrophage staining (R = 0.75, P < 0.01). CONCLUSION: GM-CSF substantially augments glycolytic flux in vitro (via a mechanism dependent on ubiquitous type 6-phosphofructo-2-kinase and tumor necrosis factor-α) and increases (18)F-FDG uptake within inflamed atheroma in vivo. These findings demonstrate that GM-CSF can be used to enhance detection of inflammation. Further studies should explore the role of GM-CSF stimulation to enhance the detection of inflammatory foci in other disease states.

Mitroflow aortic bioprosthesis 5-year follow-up: north american prospective multicenter study.

BACKGROUND: The Mitroflow valve (Sorin Group, Milan, Italy) has been in use since 1982 and has shown long-term durability in large studies from European centers but has not been studied for long-term hemodynamics in large standardized multicenter trials. This study sought to assess the hemodynamics of the Mitroflow valve by extending the duration of follow-up in an ongoing prospective multicenter trial conducted in North America. METHODS: Six sites participated in this midterm study requiring annual follow-up and echocardiographic evaluation using a standardized transthoracic echocardiography acquisition protocol. RESULTS: There were 276 patients enrolled (age 74±8 years) and 54% were in New York Heart Association (NYHA) functional class III-IV. Follow-up from the time of valve implantation had a mean of 4.0±1.7 years with a cumulative follow-up of 1,102 patient-years. At 5 years of follow-up, 99% of patients were free of moderate or severe aortic regurgitation and 94% were in NYHA functional class I or II. Between baseline and 5 years, mean gradients increased an average of 0.4 to 4.3 mm Hg. The change in effective orifice area was appreciably small (-0.1 to -0.3 cm2) after 5 years. There were 57 deaths (4 early and 53 late) and 9 valve explants. CONCLUSIONS: The Mitroflow valve implanted in the aortic position has shown to be hemodynamically stable over a 5-year follow-up in an elderly population with a high prevalence of comorbid conditions.

Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab.

Cetuximab, an antibody directed against the epidermal growth factor receptor, is an effective clinical therapy for patients with colorectal, head and neck, and non-small cell lung cancer, particularly for those with KRAS and BRAF wild-type cancers. Treatment in all patients is limited eventually by the development of acquired resistance, but little is known about the underlying mechanism. Here, we show that activation of ERBB2 signaling in cell lines, either through ERBB2 amplification or through heregulin up-regulation, leads to persistent extracellular signal-regulated kinase 1/2 signaling and consequently to cetuximab resistance. Inhibition of ERBB2 or disruption of ERBB2/ERBB3 heterodimerization restores cetuximab sensitivity in vitro and in vivo. A subset of colorectal cancer patients who exhibit either de novo or acquired resistance to cetuximab-based therapy has ERBB2 amplification or high levels of circulating heregulin. Collectively, these findings identify two distinct resistance mechanisms, both of which promote aberrant ERBB2 signaling, that mediate cetuximab resistance. Moreover, these results suggest that ERBB2 inhibitors, in combination with cetuximab, represent a rational therapeutic strategy that should be assessed in patients with cetuximab-resistant cancers.

Preventing the unpredicted: managing violence risk in mental health care.

Using clinical judgment alone, mental health professionals cannot predict individual patient violence much more accurately than chance. Clinicians could improve their prediction of violence if they routinely used structured risk assessment instruments, but they don't; the use of such tools for screening is not currently the standard of care in the United States and is not commonly reimbursed by insurance. The author argues, however, that clinicians actually can predict and prevent violence if they consider their patients as a group from the perspective of public-health epidemiology. Optimizing treatment for all patients will help prevent violence by the few who pose a risk of violence, even when such patients are not identified in advance.

Inflammatory manifestations of experimental lymphatic insufficiency.

BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

Application of robotic-assisted techniques to the surgical evaluation and treatment of the anterior mediastinum.

BACKGROUND: We report our initial experience with the application of robotic-assisted technologies to the treatment of diseases of the anterior mediastinum. METHODS: Between October 2001 and December 2003, 18 consecutive patients with anterior mediastinal masses were referred for diagnosis and treatment. Fifteen patients underwent robotic-assisted surgery with the da Vinci robotic system. A single surgical team performed all operations. Resection was accomplished by either median sternotomy or robotic-assisted techniques. RESULTS: Fourteen patients underwent successful robotic-assisted thymectomy. One patient underwent robotic-assisted biopsy of a mass that was later determined to be a poorly differentiated carcinoma, 3 patients underwent complete thymectomy by median sternotomy for biopsy-proven extracapsular thymoma, 7 patients had thymoma, and 3 had myasthenia gravis. There were 2 patients each with benign thymic cysts and thymic hyperplasia. Primary thymic carcinoid, thymolipoma, papillary thyroid cancer, and poorly differentiated carcinoma were present in 1 patient each. No conversions, intraoperative complications, or deaths occurred in the 15 patients who underwent robotic-assisted resection. The mean operative time was 96 minutes (range 62 to 132 minutes). The mean robotic time was 48 minutes (range 22 to 76). The median hospital stay was 2 days. All patients are doing well, with a median follow-up of 1 year. CONCLUSIONS: Robotic-assisted surgery of the anterior mediastinum, and particularly thymectomy, can be performed safely and efficiently. The increased visualization and instrument dexterity afforded by this technology provides an optimal minimally invasive approach to the anterior mediastinum. From this experience we have formulated a comprehensive treatment algorithm for the surgical evaluation and treatment of patients with anterior mediastinal diseases.