Search

Objectives: A prospective, multicenter study was performed to assess the safety and efficacy of the Durata and Optisure HV leads and the Ellipse VR implantable cardioverter-defibrillator (ICD) (St. Jude Medical, Sylmar, California) in a 1.5-T magnetic resonance imaging (MRI) environment. The primary safety objective was >90% freedom from MRI scan-related complications. The primary efficacy objectives were absence of change in capture threshold and absence of decrease of sensing amplitude from pre-MRI examination to 1 month after MRI., Background: MRI scanning of patients has been shown to be safe in patients with magnetic resonance-conditional implantable cardioverter-defibrillators (ICD) systems., Methods: Patients with a previously implanted magnetic resonance-conditional system underwent a nondiagnostic MRI scan. After the scan, a questionnaire was given to investigators and patients who returned for 1-month follow-up examination. A subset of patients underwent ventricular tachyarrhythmia or ventricular fibrillation (VT/VF) induction testing after the MRI to evaluate defibrillation function., Results: There were 220 patients (81% male; 62.1 ± 11.2 years of age) enrolled who received an MRI scans from 29 centers. All primary safety and efficacy endpoints were met (p < 0.0001). No significant detection delays were found in 34 patients who had VT/VF episodes after the MRI scan was performed. Most physicians reported easy and acceptable programming and ease of MRI scheduling., Conclusions: The MRI Ready MRI-conditional ICD system is safe, and electrical performance was not affected in patients receiving a 1.5-T whole-body MRI scan. Investigators reported favorable collaboration between cardiologists and radiologists in the MRI Ready IDE clinical trial. (A Clinical Evaluation of the Durata or Optisure High Voltage Leads and Ellipse VR ICD Undergoing MRI, an IDE Study [MRI Ready IDE]; NCT02787291)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Video-assisted thoracoscopic surgery (VATS) pulmonary lobectomy has been associated with decreased complication rates and length of stay compared with lobectomy by thoracotomy. No studies have addressed VATS lobectomy in Veterans Administration (VA) patients., Methods: A retrospective review was undertaken of 50 VATS lobectomies performed between August 2007 and June 2009 by one surgeon in a VA hospital, a university-affiliated county hospital, and a private community hospital., Results: VA patients had more medical comorbidities, poorer lung function, greater current smoker status, and fewer preoperative biopsies. Pleural adhesions or hilar lymphadenopathy were encountered more commonly in VA than nonfederal patients. Surgical times and number of procedures performed were greater in VA patients. There was no statistically significant difference in the risk of postoperative complications or chest tube duration although length of stay was longer for VA patients., Conclusions: VATS lobectomy is feasible in a VA setting. The evidence strongly suggests that veterans can benefit from VATS lobectomy in terms of improved outcomes and diminished length of stay compared with thoracotomy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Laparoscopic Nissen fundoplication is a common operation performed for reflux disease, generally with good results. A small percentage of patients experience transthoracic migration of the wrap, causing recurrent symptoms and eventually requiring transthoracic repair., Methods: A retrospective chart review was performed for all patients who underwent a transthoracic repair of a slipped Nissen fundoplication at our institution from 2006 to 2010. Data included demographics, previous antireflux operations, symptoms at presentation, findings at operation, and overall outcome., Results: Sixteen patients with a mean age of 61 years (range, 51-76 years) were identified who fit inclusion criteria. The most common presenting symptom was pain. Intraoperative findings included hiatal breakdown in all patients, shortened esophagus in 10 (62%) patients, and foreign body/mesh in 4 (25%) patients. Nine (56%) patients underwent a Collis gastroplasty along with a Nissen fundoplication. Nissen fundoplication alone was performed in 6 (38%) patients and a Belsey fundoplication with a Collis gastroplasty was performed in 1 (6%) patient. Minor complications occurred in 4 (25%) patients and major complications were seen in 2 (13%) patients. The median length of stay was 9 days (range, 6-30 days). There were no postoperative deaths. Overall, 12 (75%) of the patients were judged to have a good outcome, 3 (19%) a fair outcome, and 1 (6%) a poor outcome over a median 9-month follow-up., Conclusions: Transthoracic repair in patients who have had transthoracic migration of a previous Nissen fundoplication has acceptable surgical outcome and affords symptomatic relief to the majority of patients., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize a new method of postoperative gastrointestinal leak detection based on electrical resistance changes due to extravasated electrolyte contrast., Background: Postoperative gastrointestinal leak results in increased patient morbidity, mortality, and hospital costs that can be mitigated by early diagnosis. A sensitive and specific diagnostic test that could be performed at the bedside has the potential to shorten the time to diagnosis and thereby improve the quality of treatment., Materials and Methods: Anaesthetized rats underwent celiotomy and creation of a 5-mm gastrotomy. In experimental animals, electrical resistance changes were measured with a direct current ohmmeter after the introduction of 5 cc of 23.4% NaCl electrolyte solution via gavage and measured with a more sensitive alternating current ohmmeter after the gavage of 1-5 cc of 0.9% NaCl. Comparison was made to negative controls and statistical analysis was performed., Results: Leakage from the gastrotomy induced by as little as 1 cc of gavage-delivered 0.9% NaCl contrast solution was detectable as a statistically significant drop in electrical resistance when compared to results from negative controls., Conclusion: Electrical resistance change associated with electrolyte-gated leak detection is highly sensitive and specific and has the potential to be rapidly translated into clinical settings.

Lung transplantation animal models have been well established and enabled the investigation of a variety of new pharmacotherapeutic strategies for prevention of lung allograft rejection. Direct administration of immunosuppressive agents to the lung is a commonly investigated approach; however, can prove challenging due to the poor solubility of the drug molecule, the tortuous pathways of the lung periphery, and the limited number of excipients approved for inhalation. In this study, we aimed to evaluate a solubility enhancing formulation of tacrolimus for localized therapy in a lung transplanted rat model and determine the extent of drug absorption into systemic circulation. Characterization of the nebulized tacrolimus dispersion for nebulization showed a fine particle fraction (FPF) of 46.1% and a mass median aerodynamic diameter (MMAD) of 4.06 microm. After single dose administration to transplanted and non-transplanted rats, a mean peak transplanted lung concentration of 399.8+/-29.2 ng/g and mean peak blood concentration of 4.88+/-1.6 ng/mL were achieved. It is theorized that enhanced lung retention of tacrolimus is due to lipophilic associations with bronchial tissue and phospholipid surfactants in lung fluid. These findings indicate that tacrolimus dispersion for nebulization can achieve highly localized therapy for lung transplant recipients.

Tolerance to dsDNA is achieved through editing of Ig receptors that react with dsDNA. Nevertheless, some B cells with anti-dsDNA receptors escape editing and migrate to the spleen. Certain anti-dsDNA B cells that are recovered as hybridomas from the spleens of anti-dsDNA H chain transgenic mice also bind an additional, Golgi-associated antigen. B cells that bind this antigen accumulate intracellular IgM. The intracellular accumulation of IgM is incomplete, because IgM clusters are observed at the cell surface. In the spleen, B cells that express the heavy and light chains encoding this IgM are surface IgM-bright and acquire the CD21-high/CD23-low phenotype of marginal zone B cells. Our data imply that expression of an Ig that binds dsDNA and an additional antigen expressed in the secretory compartment renders B cells resistant to central tolerance. In the periphery, these B cells may be sequestered in the splenic marginal zone.

Background: Associated comorbidities in potential lung transplant recipients may significantly impact operative morbidity and mortality. We undertook this review to specifically study whether patients who underwent associated cardiac procedures either before (as a prerequisite) or during their lung transplantation had different outcomes when compared with the overall cohort of lung transplant recipients., Methods: A retrospective chart review was performed of all patients who underwent lung transplantation at the University of Texas Health Science Center at San Antonio from January 1994 to June 2004. The records of these patients were analyzed for patient-days on the ventilator, hospital length of stay, operative morbidity and mortality, and long-term survival. The patients were then divided into two groups and compared: patients who had a cardiac intervention either prerequisite to or concurrent with their transplant (group C, n = 13) and patients who did not (group NC [no cardiac intervention], n = 120)., Results: Although the median length of stay was longer in group C when compared with group NC, the number of patient-days on the ventilator and the operative morbidity and mortality were similar for both groups. Likewise, overall long-term survival was not significantly different (Kaplan-Meier method, p = 0.70)., Conclusions: Patients who are otherwise deemed to be good candidates for lung transplantation but are found to have an associated cardiac condition that could adversely affect their candidacy may still be considered for transplantation in selected cases if the cardiac abnormality can be addressed either before or during transplantation.

Firm evidence links the process of apoptosis to the induction of autoimmune disease. However, questions remain regarding the precise interactions of dying cells with the immune system. Genetic analyses indicate that deficiencies in serum proteins or receptors that mediate clearance of apoptotic cells increase the risk of autoimmunity. Moreover, administration of apoptotic cells to naive animals elicits transient autoimmune responses. Because known autoantigens are covalently modified and redistributed to cell surface blebs during the execution stage of apoptosis, increasing attention is being directed at this stage of programmed cell death, and researchers have identified a variety of autoantigens that are sequestered within blebs. However, blebs are merely a transition stage toward the complete cellular fragmentation, as blebs quickly convert into apoptotic bodies, subcellular particles (SCPs) of heterogeneous size, surface composition, and cargo. Because certain types of subcellular particles represent packets of highly enriched autoantigens, we propose that they are relevant to our understanding of autoimmunity.

The specific modification of autoantigens and their redistribution into blebs at the surface of apoptotic cells contribute to the induction of autoimmune responses. Blebs containing fragments of the apoptotic nucleus separate from the remainder of the cell to form membrane-bound sub-cellular particles (SCPs), otherwise known as apoptotic bodies. To determine whether apoptotic bodies containing nuclear antigens represent a defined subset of SCPs, we examined the heterogeneity of particles generated by Jurkat cells following synchronization of the cell cycle by serum withdrawal and inhibition of topoisomerase I by camptothecin. Particles were purified by filtration, incubated in the presence of antinucleosome or anti-cardiolipin autoantibodies, annexin V, and Sytox Orange and analyzed by flow cytometry and confocal microscopy. We demonstrate that nuclear autoantigens are associated with one clearly defined subset of SCPs that can be distinguished from other products of late apoptosis. Our experiments represent an important step towards characterizing the heterogeneity of SCPs that are generated in late apoptosis and identifying their contributions to tolerance and autoimmunity.

Mounting evidence suggests that systemic lupus erythematosus autoantigens are derived from apoptotic cells. To characterize the potential interactions between apoptotic cells and B cells, the D56R/S76R variant of 3H9, a murine autoantibody that binds to DNA, chromatin, and anionic phospholipids, was compared with DNA4/1, a human anti-DNA autoantibody. Flow cytometry revealed that only D56R/S76R bound to Jurkat cells treated with either of three distinct proapoptotic stimuli, Ab binding was dependent on caspase activity, and immunoreactivity developed subsequent to annexin V binding. Confocal microscopy established a structural basis for the distinct kinetics of binding. D56R/S76R preferentially bound to membrane blebs of apoptotic cells, whereas annexin V binding did not require blebs. Inhibition of ROCK I kinase, an enzyme that stimulates nuclear fragmentation and fragment distribution into blebs, significantly reduced Ab binding. Because members of the collectin and pentraxin families of serum proteins bind to blebs on apoptotic cells and assist in the clearance of cellular remains, our results suggest that Abs to blebs could affect the recognition of apoptotic cells by cells of the innate immune system and thus modify tolerance to nuclear Ags.