Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Critical Role for Telomerase in the Mechanism of Flow-Mediated Dilation in the Human Microcirculation.

RATIONALE: Telomerase is a nuclear regulator of telomere elongation with recent reports suggesting a role in regulation of mitochondrial reactive oxygen species. Flow-mediated dilation in patients with cardiovascular disease is dependent on the formation of reactive oxygen species. OBJECTIVE: We examined the hypothesis that telomerase activity modulates microvascular flow-mediated dilation, and loss of telomerase activity contributes to the change of mediator from nitric oxide to mitochondrial hydrogen peroxide in patients with coronary artery disease (CAD). METHODS AND RESULTS: Human coronary and adipose arterioles were isolated for videomicroscopy. Flow-mediated dilation was measured in vessels pretreated with the telomerase inhibitor BIBR-1532 or vehicle. Statistical differences between groups were determined using a 2-way analysis of variance repeated measure (n≥4; P<0.05). L-NAME (N(ω)-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor) abolished flow-mediated dilation in arterioles from subjects without CAD, whereas polyethylene glycol-catalase (PEG-catalase; hydrogen peroxide scavenger) had no effect. After exposure to BIBR-1532, arterioles from non-CAD subjects maintained the magnitude of dilation but changed the mediator from nitric oxide to mitochondrial hydrogen peroxide (% max diameter at 100 cm H2O: vehicle 74.6±4.1, L-NAME 37.0±2.0*, PEG-catalase 82.1±2.8; BIBR-1532 69.9±4.0, L-NAME 84.7±2.2, PEG-catalase 36.5±6.9*). Conversely, treatment of microvessels from CAD patients with the telomerase activator AGS 499 converted the PEG-catalase-inhibitable dilation to one mediated by nitric oxide (% max diameter at 100 cm H2O: adipose, AGS 499 78.5±3.9; L-NAME 10.9±17.5*; PEG-catalase 79.2±4.9). Endothelial-independent dilation was not altered with either treatment. CONCLUSIONS: We have identified a novel role for telomerase in re-establishing a physiological mechanism of vasodilation in arterioles from subjects with CAD. These findings suggest a new target for reducing the oxidative milieu in the microvasculature of patients with CAD.

In-vivo oesophageal regeneration in a human being by use of a non-biological scaffold and extracellular matrix.

BACKGROUND: Tissue-engineered extracellular matrix populated with autologous pluripotent cells can result in de-novo organogenesis, but the technique is complex, not widely available, and has not yet been used to repair large oesophageal defects in human beings. We aimed to use readily available stents and extracellular matrix to regenerate the oesophagus in vivo in a human being to re-establish swallowing function. METHODS: In a patient aged 24 years, we endoscopically placed a readily available, fully covered, self-expanding, metal stent (diameter 18 mm, length 120 mm) to bridge a 5 cm full-thickness oesophageal segment destroyed by a mediastinal abscess and leading to direct communication between the hypopharynx and the mediastinum. A commercially available extracellular matrix was used to cover the stent and was sprayed with autologous platelet-rich plasma adhesive gel. The sternocleidomastoid muscle was placed over the matrix. After 4 weeks, stent removal was needed due to stent migration, and was replaced with three stents telescopically aligned to improve anchoring. The stents were removed after 3·5 years and the oesophagus was assessed by endoscopy, biopsy, endoscopic ultrasonography, and high-resolution impedance manometry. FINDINGS: After stent removal we saw full-thickness regeneration of the oesophagus with stratified squamous epithelium, a normal five-layer wall, and peristaltic motility with bolus transit. 4 years after stent removal, the patient was eating a normal diet and maintaining a steady weight. INTERPRETATION: Maintenance of the structural morphology of the oesophagus with off-the-shelf non-biological scaffold and stimulation of regeneration with commercially available extracellular matrix led to de-novo structural and functional regeneration of the oesophagus. FUNDING: None.

When the Gastrointestinal Conduit for Total Esophageal Reconstruction Is Not an Option: Review of the Role of Skin Flaps and Report of Salvage With a Single-Stage Tubed Anterolateral Thigh Flap.

This review adds to the limited body of literature describing the use of skin flaps for reconstruction of the esophagus and includes a report of a successful 1-stage, intrathoracic reconstruction of the cervical and thoracic esophagus after failed gastrointestinal conduit. Already widely used for reconstruction of the pharynx and cervical esophagus, the versatile anterolateral thigh flap can be considered an option for more extensive defects of the cervical and thoracic esophagus in this challenging patient population when gastric, jejunal, or colon conduits are not available. The authors believe the anterolateral thigh flap should be considered in 1-stage anatomic reconstruction of the cervical and thoracic esophagus in the absence of feasible gastrointestinal conduits.

Robotic-enhanced hybrid ablation for persistent and long-standing atrial fibrillation: Early assessment of feasibility, safety, and efficacy.

Objectives: To assess feasibility, safety, and early efficacy of robotic-enhanced epicardial ablation (RE-EA) as first stage of a hybrid approach to patients with persistent (PsAF) and long-standing atrial fibrillation (LSAF). Methods: Single-center, retrospective analysis of patients with documented PsAF and LSAF who underwent RE-EA followed by catheter-guided endocardial ablation. Postoperatively, patients were monitored for major adverse events and underwent rhythm follow-up at 3 and 12 months. Results: Between January 2021 and June 2023, we performed RE-EA in 64 patients (73.5% male, CHA2DS2-VASc 2.7 ± 1.6, BMI 34.1 ± 6.3 kg/m2). Mean AF preoperative duration and left atrial volume index were, respectively, 85 months and 47.5 mL/m2. Through the robotic approach, the intended lesion set was completed in all patients without cardiopulmonary bypass support, conversion to thoracotomy/sternotomy, blood transfusions, or perioperative mortality. The average LOS was 1.7 days, with only 1 patient requiring intensive care unit admission and >65% of patients discharged within 24 hours. At follow-up, 2 (3.1%) patients experienced new left pleural effusion or hemidiaphragm paralysis requiring treatment. There were no readmissions related to AF, stroke, thromboembolic events, or deaths. The mean interval between the epicardial and endocardial stages of the procedure was 5.9 months. Rhythm follow-up showed AF resolution in 73.4% and 71.9% of patients at 3 and 12 months, respectively. Conclusions: RE-EA is a feasible and safe, first-stage approach for the treatment of patients with PsAF and LSAF. It improves exposure of the intended targets, favors short hospital stay, and facilitates return to activity with satisfactory AF treatment in the short term.

A Case of Unicentric Castleman Disease with Concomitant Myasthenia Gravis and Persistent Left Superior Vena Cava.

BACKGROUND Castleman disease was first described in 1956 as mediastinal masses composed of benign lymphoid hyperplasia with germinal center formation and capillary proliferation closely resembling thymomas. It has been linked with many multi-system disorders, including myasthenia gravis. Cases of Castleman disease with corresponding myasthenia gravis have higher rates of postoperative myasthenic crisis, which are reported as high as 37.5%. We encountered a case of Castleman disease with myasthenia gravis that was discovered early and managed successfully with complete surgical resection and no postoperative myasthenic crisis. CASE REPORT A 25-year-old woman with an uncomplicated history presented with shortness of breath, numbness in hands, tiring with chewing, and fatigue. Myasthenia gravis was diagnosed with serology test results, and a 7.5×7.0-cm mediastinal mass was discovered in addition to the incidental finding of a persistent left superior vena cava, closely abutting the mass. Biopsy showed lymphoid proliferation, regressed germinal centers surrounded by small lymphocytes, and vascular proliferation, consistent with unicentric Castleman disease, hyaline-vascular type. The patient was successfully treated for Castleman disease with myasthenia gravis, and no postoperative myasthenic crisis occurred. CONCLUSIONS Castleman disease associated with myasthenia gravis can dramatically increase the risk of postoperative myasthenic crisis. Our literature review of all 16 cases of Castleman disease with myasthenia gravis since 1973 revealed that 18.75% of cases were associated with a postoperative myasthenic crisis. This association elicits the importance of prompt diagnosis of myasthenia gravis when evaluating mediastinal masses and the value of having neurology and anesthesiology staff aware of the increased risk of crisis.

Definitive Chemoradiation Associated with Improved Survival Outcomes in Patients with Synchronous Oligometastatic Esophageal Cancer.

BACKGROUND: The study of oligometastatic esophageal cancer (EC) is relatively new. Preliminary data suggests that more aggressive treatment regimens in select patients may improve survival rates in oligometastatic EC. However, the consensus recommends palliative treatment. We hypothesized that oligometastatic esophageal cancer patients treated with a definitive approach (chemoradiotherapy [CRT]) would have improved overall survival (OS) compared to those treated with a purely palliative intent and historical controls. METHODS: Patients diagnosed with synchronous oligometastatic (any histology, ≤5 metastatic foci) esophageal cancer treated in a single academic hospital were retrospectively analyzed and divided into definitive and palliative treatment groups. Definitive CRT was defined as radiation therapy to the primary site with ≥40 Gy and ≥2 cycles of chemotherapy. RESULTS: Of 78 Stage IVB (AJCC 8th ed.) patients, 36 met the pre-specified oligometastatic definition. Of these, 19 received definitive CRT, and 17 received palliative treatment. With a median follow-up of 16.5 months (Range: 2.3-95.0 months), median OS for definitive CRT and palliative groups were 90.2 and 8.1 months (p < 0.01), translating into 5-year OS of 50.5% (95%CI: 32.0-79.8%) vs. 7.5% (95%CI: 1.7-48.9%), respectively. CONCLUSIONS: Oligometastatic EC patients treated with definitive CRT benefited from that approach with survival rates (50.5%) that vastly exceeded historical standards of 5% at 5 years for metastatic EC. Oligometastatic EC patients treated with definitive CRT had significantly improved OS compared to those treated with palliative-only intent within our cohort. Notably, definitively treated patients were generally younger and with better performance status versus those palliatively treated. Further prospective evaluation of definitive CRT for oligometastatic EC is warranted.

Is intrathoracic rib plate fixation advantageous over extrathoracic plating? A biomechanical cadaveric study.

BACKGROUND: The high morbidity following surgical interventions on the chest wall because of large incisions often prevents surgeons from operative rib fracture treatment. Minimally invasive approaches to the intrathoracic side of the rib could allow for smaller incisions with lower morbidity while maintaining stability of fixation. The aim of this study was to explore the biomechanical competence of intrathoracic versus extrathoracic plating in a human cadaveric rib fracture model and investigate the effect of plating using two versus three screws per fracture fragment. METHODS: Twenty pairs of fresh-frozen human cadaveric ribs from elderly female donors aged 82.4 ± 7.8 years were used. First, the stiffness of each native rib was calculated via nondestructive (2 N-5 N) biomechanical testing under two loading conditions: ramped two-point bending and combined ramped tensile bending with torsional loading. Second, the ribs were fractured under three-point bending with their intrathoracic side put under tensile stress. Third, specimens were assigned to four groups (n = 10) for either intrathoracic or extrathoracic plating with two or three screws per fragment. Following instrumentation, all ribs were dynamically tested over 400,000 cycles under combined sinusoidal tensile bending with torsional loading (2 N-5 N at 3 Hz). Finally, all specimens were destructively tested under ramped two-point bending. RESULTS: Following instrumentation and cyclic testing, significantly higher construct stiffness was observed for intrathoracic vs. extrathoracic plating under anatomical loading conditions (p ≤ 0.03). No significant differences were detected for implant subsidence after plating with two or three screws per fragment (p ≥ 0.20). CONCLUSION: This study demonstrates significantly higher construct stiffness following intrathoracic over extrathoracic plating, thus indicating superior plate support of the former. In the clinical context, using only two instead of three screws per fragment not only could maintain stability of fixation but also decrease surgery time and costs, and allow for smaller incisions with lower morbidity. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Use of the Internet to Facilitate an Annual Scientific Meeting: A Report of the First Virtual Chest Wall Injury Society Summit.

INTRODUCTION: The COVID-19 pandemic has resulted in cancellation of medical peer meetings. The Chest Wall Injury Society Annual Summit was scheduled for April 2020. Due to safety concerns, the Society altered the meeting to an online format. The purpose of this paper is to describe how this was accomplished and also to highlight its outcomes. METHODS: An online survey of participants was carried out to assess their views on the educational yield and technical difficulties encountered as compared to in-person meetings. RESULTS: Sixty two of 275 (23%) registered participants filled out the survey. Eighty four percent felt that the educational quality was excellent/good. Seventy five percent and 95% felt in-person meetings are better for education and for networking, respectively. Eighty seven percent preferred in-person meetings in the future but would attend a virtual meeting again. Thirteen percent had technical difficulties accessing the meeting. CONCLUSION: Online meetings are feasible but in-person meetings have more educational and networking value.

The Chest Wall Injury Society Recommendations for Reporting Studies of Surgical Stabilization of Rib Fractures.

BACKGROUND: Publications investigating the efficacy of surgical stabilization of rib fractures (SSRF) have increased exponentially. However, there is currently no standardized reporting structure for these studies, rendering both comparisons and extrapolation problematic. METHODS: A subject matter expert group was formed by the Chest Wall Injury Society. This group conducted a review of the SSRF investigational literature and identified variable reporting within several general categories of relevant parameters. A compliment of guidelines was then generated. RESULTS: The reporting guidelines consist of 26 recommendations in the categories of: (1) study type, (2) patient and injury characteristics, (3) patient treatments, (4) outcomes, and (5) statistical considerations. CONCLUSION: Our review identified inconsistencies in reporting within the investigational SSRF literature. In response to these inconsistencies, we propose a set of recommendations to standardize reporting of original investigations into the efficacy of SSRF.

Dickkopf-1 (DKK1) promotes tumor growth via Akt-phosphorylation and independently of Wnt-axis in Barrett's associated esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is still associated with poor prognosis, despite modern multi-modal therapies. New molecular markers, which control cell cycle and promote lymph node metastases or tumor growth, may introduce novel target therapies. Dickkopf-1 (DKK1) is a secreted glycoprotein that blocks the oncogenic Wnt/ß-catenin signaling and its aberrant expression has been observed in many malignancies, including EAC. In this study, we investigated the biological role of DKK1 in EAC. Analysis of DKK1 and active ß-catenin expression in human esophageal tissues confirmed a simultaneous DKK1-overexpression together with aberrant activation of ß-catenin signaling in EAC in comparison with Barrett's and healthy mucosa. To elucidate the molecular role of DKK1, the OE33 adenocarcinoma cells, which were found to overexpress DKK1, were subjected to functional and molecular assays following siRNA-mediated DKK1-knockdown. At the functional level, OE33 cell viability, proliferation, migration and invasion were significantly attenuated by the absence of DKK1. At the molecular level, neither DKK1-knockdown nor application of exogenous recombinant DKK1 were found to alter the baseline ß-catenin signaling in OE33 cells. However, DKK1-knockdown significantly abrogated downstream Akt-phosphorylation. On the other hand, the Wnt-agonist, Wnt3a, restored the Akt-phorphorylation in the absence of DKK1, without, however, being able to further stimulate ß-catenin transcription. These findings suggest that the ß-catenin transcriptional activity in EAC is independent of Wnt3a/DKK1 site-of-action and define an oncogenic function for DKK1 in this type of malignancy via distinct activation of Akt-mediated intracellular pathways and independently of Wnt-axis inhibition. Taken together, DKK1 may present a novel therapeutic target in EAC.

Atrial fibrillation after transhiatal esophagectomy with transcervical endoscopic esophageal mobilization: one institution's experience.

BACKGROUND: There have been numerous studies regarding atrial fibrillation (AF) associated with cardiac and pulmonary surgery; however, studies looking at esophagectomy and atrial fibrillation are sparse. The goal of this study was to review our institution's atrial fibrillation rate following esophagectomy in order to better define the incidence and predisposing factors in this patient population. METHODS: A retrospective chart review of all patients undergoing esophagectomy with transcervical endoscopic mobilization of the esophagus (TEEM) at the Medical College of Wisconsin and Affiliated Hospitals from July 2009 through December 2012. RESULTS: Seventy-one patients underwent TEEM esophagectomy during the study period. Of those, 23 (32.4%) patients developed new atrial fibrillation postoperatively. ICU (Intensive Care Unit) length of stay was 7.1 days for those that did not receive amiodarone, compared to 5.3 days for those that did receive amiodarone (p < 0.025). Those that went into AF spent on average 9.3 days in the ICU compared to 4.7 days for their counterparts that did not go into AF (p < 0.006). Total length of stay was not statistically different between populations [15.1 +/- 11.3 days compared to 13.5 +/- 9.4 days for those who did not go into AF (p < 0.281)]. Receiving preoperative amiodarone was found to reduce the overall incidence of AF. There was a trend towards decreased risk of going into AF in those who received preoperative amiodarone with an adjusted hazard ratio of 0.555 (p = 0.057). CONCLUSION: Similar to data reported in previous literature, postoperative atrial fibrillation was found to increase ICU length of stay as well as overall length of hospital stay. Preoperative amiodarone administration displayed a trend toward decreasing the rates of atrial fibrillation in patients undergoing TEEM.

Primary pulmonary leiomyosarcoma with invasion of the pulmonary vein-A case report.

INTRODUCTION: Primary pulmonary leiomyosacromas are a subset of the rare sarcomatous lung neoplasms, found to be less than 0.5% of the organ's primary malignant tumors (Attanoos et al., 1996). PRESENTATION OF CASE: We describe here a case of a 69-year-old woman who presented with heart palpitations, incidentally found to have a large lung mass abutting the left inferior pulmonary veins. Challenging tissue diagnosis led to invasive alternatives; attempted full neoplastic resection and pneumonectomy. DISCUSSION: The mainstay of treatment for these tumors is complete surgical resection. Chemotherapy and radiation can be helpful adjuncts as well. CONCLUSION: This case presents a unique invasion pattern of a primary leiomyosarcoma of the lung, our diagnostic process, and surgical intervention.

Roux-en-Y diversion for debilitating reflux after esophagectomy.

Two patients with debilitating reflux after esophagectomy are reported. Complete relief of symptoms after creation of a Roux-en-Y limb to the gastric conduit is described.

A novel approach to the management of tracheoinnominate artery fistula.

A 75-year-old gentleman with tracheoinnominate fistula is reported. The issues regarding the surgical approach to this problem are reviewed and a creation of an aorto-axillary bypass graft described.

First nationwide survey of US integrated 6-year cardiothoracic surgical residency program directors.

OBJECTIVE: The recently implemented integrated 6-year (I-6) format represents a significant change in cardiothoracic surgical residency training. We report the results of the first nationwide survey assessing I-6 program directors' impressions of this new format. METHODS: A 28-question web-based survey was distributed to program directors of all 24 Accreditation Council for Graduate Medical Education-accredited I-6 training programs in November 2013. The response rate was a robust 67%. RESULTS: Compared with graduates of traditional residencies, most I-6 program directors with enrolled residents believed that their graduates will be better trained (67%), be better prepared for new technological advances (67%), and have superior comprehension of cardiothoracic disease processes (83%). Just as with traditional program graduates, most respondents believed their I-6 graduates would be able to independently perform routine adult cardiac and general thoracic operations (75%) and were equivocal on whether additional specialty training (eg, minimally invasive, heart failure, aortic) was necessary. Most respondents did not believe that less general surgical training disadvantaged I-6 residents in terms of their career (83%); 67% of respondents would have chosen the I-6 format for themselves if given the choice. The greater challenges in training less mature and experienced trainees and vulnerability to attrition were noted as disadvantages of the I-6 format. Most respondents believed that I-6 programs represent a natural evolution toward improved residency training rather than a response to declining interest among medical school graduates. CONCLUSIONS: High satisfaction rates with the I-6 format were prevalent among I-6 program directors. However, concerns with respect to training relatively less experienced, mature trainees were evident.

Reconstruction of the right atrium using an extracellular matrix patch in a patient with severe mediastinal aspergillosis.

INTRODUCTION: We report a case of reconstruction of the right atrial wall using a novel bioresorbable patch derived from porcine small intestinal submucosa. PRESENTATION OF CASE: Our patient presented with mediastinal aspergillosis as a result of chronic steroid therapy for an oligodendroglioma. Hemodynamic compromise and syncopal episodes secondary to the mass effect of the aspergilloma prolapsing through tricuspid valve necessitated palliative surgical excision. DISCUSSION: Intraoperatively, it was confirmed that the lesion had eroded into the right atrium and partially occluded right ventricular inflow. In order to achieve appropriate palliation a wide resection of the atrial wall was necessary. The atrial reconstruction was then performed using an extracellular matrix-derived biopatch. This case was further complicated by postoperative bleeding requiring re-operation. CONCLUSION: We describe the methods used for repair using a novel patch in this rare case of invasive aspergillosis extending into the right atrium and resulting in compromise of diastolic right ventricular filling.