Association of preprocedural ultrashort-term heart rate variability with clinical outcomes after transcatheter aortic valve replacement: A nested, case-control, pilot study.

Background: Because heart rate variability (HRV) has been linked to important clinical outcomes in various cardiovascular disease states, we investigated whether preprocedural ultrashort-term HRV (UST-HRV) differs between 1-year survivors and nonsurvivors after transcatheter aortic valve replacement (TAVR). Methods: In our single-center, retrospective, nested pilot study, we analyzed data from patients with severe aortic stenosis undergoing TAVR. All patients had preprocedural UST-HRV measured before the administration of any medications or any intervention. To investigate whether preprocedural HRV is associated with 1-year survival, we performed a logistic regression analysis controlling for Kansas City Cardiomyopathy Questionnaire 12 score. Results: In our parent cohort of 100 patients, 42 patients (28 survivors and 14 nonsurvivors) were included for analysis. Root mean square of successive differences (RMSSD) and standard deviation of NN intervals (SDNN) were lower in patients who survived to 1-year post TAVR compared to nonsurvivors [10 (IQR 8-23) vs 23 (IQR 17-33), P = 0.04 and 10 (IQR 7-16) vs 17 (IQR 11-40), P = 0.03, respectively]. Logistic regression demonstrated a trend in the association of preprocedure RMSSD with 1-year mortality and a 5% higher risk of 1-year mortality with each unit increment in UST-HRV using SDNN (OR 1.05; 95%CI 1.01-1.09, P = 0.02). Conclusion: Our data suggest an inverse relationship between preprocedural UST-HRV and 1-year survival post-TAVR. This finding highlights the potential complexity of HRV regulation in chronic vs acute illness. Prospective studies are needed to validate our findings and to determine whether UST-HRV can be used for risk stratification in patients with severe aortic stenosis.

Color Doppler Artifact Masking Iatrogenic Aortic Valve Injury Related to an Impella Device.

The Impella (Abiomed, Danvers, MA) is a minimally invasive transvalvular left ventricular assist device (LVAD) that effectively unloads the left ventricle (LV), especially in patients with ventricular arrhythmias in the setting of a venous-arterial extracorporeal membrane oxygenator (VA ECMO).1,2 Utilization of the Impella device has increased significantly in the last few years for high-risk percutaneous coronary intervention and cardiogenic shock because of its relatively easy implantation in the catheterization lab and the operating room. Although rare, iatrogenic injury of the aortic valve (AV) can be caused by placement of the device across the AV.3 This can lead to aortic regurgitation (AR) with significant clinical consequences in the setting of cardiogenic shock. This AR can be challenging to diagnose echocardiographically because of the artifacts generated by the device when using color-flow Doppler. In this E-challenge, the authors emphasize the importance of recognizing these findings for accurate interpretation of the echocardiogram in the management of cardiogenic shock refractory to the Impella LVAD and the utility of transesophageal echocardiography (TEE).

Transient Aphonia After Mediastinoscopy.

The most common adverse event after cervical mediastinoscopy is recurrent laryngeal nerve (RLN) injury, which has an incidence of 0.6% [1]. We report the case of a 68-year-old man with non-small cell lung cancer (NSCLC) who experienced transient bilateral vocal cord paralysis after mediastinoscopy, which manifested in complete aphonia. This patient's ability to maintain his airway was carefully followed up, but neither endotracheal intubation nor tracheostomy was required. The vocal cord paralysis resolved without intervention after 5 hours. To our knowledge, this is the first reported case in which bupivicaine used at the end of a cervical mediastinoscopy diffused through the freshly dissected planes to paralyze both RLNs along the tracheoesophageal grooves.

Evaluation of an interactive science publishing tool: toward enabling three-dimensional analysis of medical images.

RATIONALE AND OBJECTIVES: Higher resolution medical imaging platforms are rapidly emerging, but there is a challenge in applying these tools in a clinically meaningful way. The purpose of the current study was to evaluate a novel three-dimensional (3D) software imaging environment, known as interactive science publishing (ISP), in appraising 3D computed tomography images and to compare this approach with traditional planar (2D) imaging in a series of lung cancer cases. MATERIALS AND METHODS: Twenty-four physician volunteers at different levels of training across multiple specialties were recruited to evaluate eight lung cancer-related clinical vignettes. The volunteers were asked to compare the performance of traditional 2D versus the ISP 3D imaging in assessing different visualization environments for diagnostic and measurement processes and to further evaluate the ISP tool in terms of general satisfaction, usability, and probable applicability. RESULTS: Volunteers were satisfied with both imaging methods; however, the 3D environment had significantly higher ratings. Measurement performance was comparable using both traditional 2D and 3D image evaluation. Physicians not trained in 2D measurement approaches versus those with such training demonstrated better performance with ISP and preferred working in the ISP environment. CONCLUSIONS: Recent postgraduates with only modest self-administered training performed equally well on 3D and 2D cases. This suggests that the 3D environment has no reduction in accuracy over the conventional 2D approach, while providing the advantage of a digital environment for cross-disciplinary interaction for shared problem solving. Exploration of more effective, efficient, self-directed training could potentially result in further improvement in image evaluation proficiency and potentially decrease training costs.

Circulating angiogenesis biomarkers are associated with disease progression in lung adenocarcinoma.

BACKGROUND: Dysregulation of angiogenesis is known to be associated with tumorigenesis and metastatic progression in multiple carcinomas. The aim of this study was to evaluate the prognostic value of circulating angiogenesis biomarkers in lung adenocarcinoma progression. For that, we hypothesize that circulating levels of biomarkers characteristic for discrete processes within angiogenesis are associated with specific phases of disease progression. Appreciation of these profiles may have important implications for disease detection and prognostication. METHODS: Patients with lung adenocarcinoma enrolled in the study were grouped as follows: node negative (T1a-3N0M0; n = 69), node positive (T1a-4N1-2M0; n = 60), and disseminated disease (TxNxM1; n = 68). All serum specimens were assayed for 17 angiogenesis biomarkers on the Luminex platform and statistically evaluated by analysis of variance for median differences in biomarker concentration at distinct phases of disease progression and by log rank methods for associations with clinical outcome. RESULTS: We found circulating hepatocyte growth factor, heparin-binding epidermal growth factor, epidermal growth factor, and vascular endothelial growth factor-C levels significantly elevated (p < 0.05) in patients with node positive versus node negative disease. Similarly, median serum concentrations of bone morphogenic protein-9, endoglin, fibroblast growth factor-1, fibroblast growth factor-2, interleukin-8, placental growth factor, vascular endothelial growth factor-C, and vascular endothelial growth factor-D were significantly (p < 0.05) higher in patients with disseminated disease than in patients with node positive disease. Five biomarkers total were strongly prognostic (p < 0.05) for overall survival in the node negative cohort. CONCLUSIONS: Angiogenesis is a process central to lung adenocarcinoma progression. We describe the modulation in serum angiogenesis biomarker concentrations through the various phases of non-small cell lung cancer progression. Additional refinement efforts are under way to enhance test performance, followed by additional validation studies.

Development and validation of a plasma biomarker panel for discerning clinical significance of indeterminate pulmonary nodules.

INTRODUCTION: The recent findings of the National Lung Screening Trial showed 24.2% of individuals at high risk for lung cancer having one or more indeterminate nodules detected by low-dose computed tomography-based screening, 96.4% of which were eventually confirmed as false positives. These positive scans necessitate additional diagnostic procedures to establish a definitive diagnosis that adds cost and risk to the paradigm. A plasma test able to assign benign versus malignant pathology in high-risk patients would be an invaluable tool to complement low-dose computed tomography-based screening and promote its rapid implementation. METHODS: We evaluated 17 biomarkers, previously shown to have value in detecting lung cancer, against a discovery cohort, comprising benign (n = 67) cases and lung cancer (n = 69) cases. A Random Forest method based analysis was used to identify the optimal biomarker panel for assigning disease status, which was then validated against a cohort from the Mayo Clinic, comprising patients with benign (n = 61) or malignant (n = 20) indeterminate lung nodules. RESULTS: Our discovery efforts produced a seven-analyte plasma biomarker panel consisting of interleukin 6 (IL-6), IL-10, IL-1ra, sIL-2Rα, stromal cell-derived factor-1α+ß, tumor necrosis factor α, and macrophage inflammatory protein 1 α. The sensitivity and specificity of our panel in our validation cohort is 95.0% and 23.3%, respectively. The validated negative predictive value of our panel was 93.8%. CONCLUSION: We developed a seven-analyte plasma biomarker panel able to identify benign nodules, otherwise deemed indeterminate, with a high degree of accuracy. This panel may have clinical utility in risk-stratifying screen-detected lung nodules, decrease unnecessary follow-up imaging or invasive procedures, and potentially avoid unnecessary morbidity, mortality, and health care costs.

Development of a serum biomarker panel predicting recurrence in stage I non-small cell lung cancer patients.

OBJECTIVE: Molecular diagnostics capable of prognosticating disease recurrence in stage I non-small cell lung cancer (NSCLC) patients have implications for improving survival. The objective of the present study was to develop a multianalyte serum algorithm predictive of disease recurrence in stage I NSCLC patients. METHODS: The Luminex immunobead platform was used to evaluate 43 biomarkers against 79 patients with resectable NSCLC, with the following cohorts represented: stage I (T(1)-T(2)N(0)M(0)) NSCLC without recurrence (n = 37), stage I (T(1)-T(2)N(0)M(0)) NSCLC with recurrence (n = 15), and node-positive (T(1)-T(2)N(1)-N(2)M(0)) NSCLC (n = 27). Peripheral blood was collected before surgery, with all patients undergoing anatomic resection. Univariate statistical methods (receiver operating characteristics curves and log-rank test) were used to evaluate each biomarker with respect to recurrence and outcome. Multivariate statistical methods were used to develop a prognostic classification panel for disease recurrence. RESULTS: No relationship was found between recurrence and age, gender, smoking history, or histologic type. Analysis for all stage I patients revealed 28 biomarkers significant for recurrence. Of these, the log-rank test identified 10 biomarkers that were strongly (P < .01) prognostic for recurrence. The Random Forest algorithm created a 6-analyte panel for preoperative classification that accurately predicted recurrence in 77% of stage I patients tested, with a sensitivity of 74% and specificity of 79%. CONCLUSIONS: We report the development of a serum biomarker algorithm capable of preoperatively predicting disease recurrence in stage I NSCLC patients. Refinement of this panel might stratify patients for adjuvant therapy or aggressive recurrence monitoring to improve survival.

Video-assisted thoracoscopic trisegmentectomy and left upper lobectomy provide equivalent survivals for stage IA and IB lung cancer.

OBJECTIVES: Despite a trend toward sublobar resections for lung cancers, some question the adequacy of limited resections in the treatment of lung cancer and questions remain about performing these procedures by video-assisted thoracoscopic surgery (VATS). We compared the survival for lung cancers treated with VATS segmentectomy versus VATS lobectomy. METHODS: VATS segmentectomy and lobectomy for both malignant and benign lung pathology are reviewed from a single institution. RESULTS: Between 1998 and 2010, 73 VATS trisegmentectomies were performed in 49 women and 24 men (mean age, 72 years). Diagnoses included primary lung cancer (91%), benign disease (4%), and metastatic disease (5%). Primary lung cancers were 68% for stage IA, 17% for stage IB, and 15% for stage II-IV. Seventy-three left upper lobe (LUL) trisegmentectomies were performed. Mean hospital stay after VATS trisegmentectomy was 3.8 days, versus 5.5 days after VATS LUL lobectomy (P = .0736). Complication rates for trisegmentectomy group (37%) and lobectomy (17%; P > .05) were not statistically different. Survival after VATS trisegmentectomy and LUL lobectomy for either stage IA lung cancer or stage IB lung cancer was not statistically significant. CONCLUSIONS: Segmentectomy can be performed by VATS with no greater morbidity and mortality than with VATS lobectomy. LUL trisegmentectomy provides the same survival as lobectomy for stage IA and IB tumors. Our experience supports the use of lingular-sparing trisegmentectomy in the treatment of stage IA and IB lung cancer.

Anterior mediastinal mass secondary to histoplasmosis.

Histoplasmosis in the mediastinum is an uncommon diagnosis that presents similarly to other benign and neoplastic conditions encountered in the chest. Here we describe a 36-year-old woman who presented with dyspnea secondary to a large anterior mediastinal mass that was biopsy and culture negative for neoplasm or infection. Video-assisted thoracoscopic surgery biopsy confirmed a large anterior mediastinal mass adherent to the aorta, which contained foci of histoplasmosis species. She is currently undergoing a long postoperative course of itraconozole and an empiric course of oral steroids to prevent development of fibrosing mediastinitis.

Adenocarcinoma in a 40-year-old colonic interposition treated with Ivor Lewis esophagectomy and esophagogastric anastomosis.

Colon interposition for benign stricture is associated with significant perioperative complications that carry high morbidity and mortality, but long-term sequelae such as further strictures and colonic redundancy are often well-tolerated. These benign complications are frequently described in literature, but adenocarcinoma in the colonic graft is a rare complication. We describe a 60-year-old man with a history of benign esophageal stricture who was treated with colon interposition 40 years ago and presented with dysphagia secondary to stage 1 colon graft adenocarcinoma. He was successfully treated with an Ivor Lewis esophagectomy and primary esophagogastric anastomosis.

Biomarkers of the insulin-like growth factor pathway predict progression and outcome in lung cancer.

BACKGROUND: Insulin-like growth factor 1 (IGF-I), IGF binding proteins (IGFBP) 1 to 7, and C-peptide have been postulated to predict survival in non-small cell lung cancer (NSCLC). Studying serum levels in NSCLC patients treated with surgical resection may provide information on the aggressiveness of tumors and be predictive of disease recurrence. METHODS: Immunobead assays were used to measure pretreatment serum levels of IGF-I, IGFBP1 to IGFBP7, and C-peptide in 100 NSCLC patients. Of these, 59 had no metastatic progression (T1 to T4 N0 M0), whereas 41 had positive lymph nodes (T1 to T4 N1 to N3 M0). Data were analyzed using the Mann-Whitney two-sided rank sum test or Kaplan-Meier curves. RESULTS: Low serum IGFBP5 levels correlated strongly with a positive nodal status (p < 0.001) and any incidence of disease recurrence (p = 0.003). Low serum levels of IGFBP5 also predicted poor recurrence-free survivals in the overall cohort (p ≤ 0.001) and in patients with no nodal metastases (p = 0.027). Conversely, a high serum level of IGFBP7 correlated with positive nodal status (p = 0.008), but was not prognostic for recurrence-free survival. No significant correlations were found for IGFBP5 or IGFBP7 for sex, age, race, smoking history, tumor histology, or fasting state. CONCLUSIONS: IGFBP5 and IGFBP7 had value as biomarkers for identifying NSCLC progression and patient outcome.

A large pleural effusion in a patient receiving peritoneal dialysis.

Hydrothorax as a complication of peritoneal dialysis (PD) is a rare but recognized event. Proposed mechanisms for the development of a pleuro-peritoneal communication include congenital diaphragmatic defects, acquired weakening of diaphragmatic fibers caused by high intra-abdominal pressures during peritoneal dialysis, and impairments in lymphatic drainage. Pleural fluid analysis and diagnostic imaging assist in differentiation from other causes of pleural effusion. Nearly 50% of patients with this diagnosis have resolution of hydrothorax after temporary cessation of PD with interim hemodialysis for 2-6 weeks. Historically, other treatment options have included conventional pleurodesis and open thoracotomy with direct repair, producing variable results. With the advent of video-assisted thoracoscopy (VATS), surgical repairs and pleurodesis are now frequently performed under direct visualization with minimal invasiveness. We report a case of hydrothorax in a patient after recent introduction to peritoneal dialysis. Pleuro-peritoneal communication was documented with thoracentesis and radionuclide scanning. VATS pleurodesis with talc was performed. Repeat scintigraphy performed 1 week after the procedure revealed no residual communication, and patient was able to resume PD without further complications.