Value of perioperative inhaled epoprostenol with low tidal volume ventilation for complex endocarditis surgery.

BACKGROUND AND AIM: To compare outcomes of patients treated with inhaled epoprostenol and low tidal volume ventilation during cardiopulmonary bypass with those who did not receive this medication in the operating room at all, and those who received it as a rescue therapy at the end of the case. METHODS: Retrospective chart review between 2014 and 2017, follow-up included the entire hospital stay. RESULTS: Seventy-one patients were included, and mean age was 54 years. 78.9% of the patients were male. Procedures included 96% (n = 68) aortic valve replacement, 28% (n = 20) reconstruction of the intravalvular fibrosa, and 13% (n = 9) repair of an endocarditis-related intracardiac fistula. Patients who received epoprostenol (iEpo) (treatment and rescue groups), when compared with the control group had more intra-aortic balloon pump placement (23% vs 2.5%, P = .018), open chest after surgery (32% vs 7.5%, P = .012), and duration of mechanical ventilation (8.3 ± 2.7 vs. 2.4 ± 0.4 days, P = 0.01). There was no significant difference between the two groups in terms of extracorporeal circulatory support (6.5% vs 2.5%, P = .577) and hospital death (13% vs 10%, P = .72). In a subanalysis, hospital death and duration of mechanical ventilation were higher in the recue group when compared with the treatment group (P = .004 and .056, respectively). CONCLUSIONS: Prophylactic application of iEpo with low tidal volume ventilation for an anticipated complex endocarditis operation may contribute to favorable outcome when compared with postoperative epoprostenol rescue.

Long-term Outcomes of Surgery for Invasive Valvular Endocarditis Involving the Aortomitral Fibrosa.

BACKGROUND: Reconstruction of the intervalvular fibrosa (IVF) for invasive double-valve infective endocarditis (IE) is a technically challenging operation. This study presents the long-term outcomes of two surgical techniques for IVF reconstruction. METHODS: From 1988 to 2017, 138 patients with invasive double-valve IE underwent surgical reconstruction of the IVF, along with double-valve replacement (Commando procedure, n = 86) or aortic valve replacement with mitral valve repair (hemi-Commando procedure, n = 52). Mean follow-up was 41 ± 5.9 months. RESULTS: Reoperation was required in 82% of patients, and 34% underwent emergency surgery. Pathologic features included positive blood cultures (90%), prosthetic valve IE (75%), aortic root abscess (78%), mitral annular abscess (24%), and intracardiac fistula (12%). There were 28 hospital deaths: 21 (24%) in the Commando group and 7 (14%) in the hemi-Commando group (P = .12). Overall survival at 1, 5, and 10 years was 67%, 48%, and 37%, respectively. Coronary artery disease, native valve IE, and causative organism (Staphylococcus aureus, coagulase-negative Staphylococcus, and viridans streptococci) were risk factors for late mortality. Freedom from reoperation at 1, 5, and 8 years was 87%, 74%, and 55%, respectively. Freedom from recurrent IE at 1, 5, and 8 years was 90%, 78%, and 67%, respectively. CONCLUSIONS: Although it is technically demanding, surgery for invasive IE involving IVF, which provides the only chance for cure, can be performed with reasonable clinical outcomes. In cases of IE invading the IVF and limited to the anterior mitral valve leaflet, a hemi-Commando procedure that includes mitral valve repair has improved early outcomes.

Patterns of Recurrence and Overall Survival in Incidental Lung Cancer in Explanted Lungs.

BACKGROUND: Recurrence and overall survival for incidental lung cancer in explanted lungs vary between different series. Recurrence patterns are also not well described. The primary objective of this study is to study the recurrence patterns and time to recurrence for various stages of lung cancer in lung transplant recipients. METHODS: A retrospective review of our institutional database was performed to identify patients who had incidental lung cancer found in transplant pneumonectomy specimens from 1990 to 2017. Demographic, radiographic, and perioperative clinical variables were collected. Time to recurrence, overall survival, and recurrence patterns were recorded. Freedom from recurrence and overall survival were estimated by using Kaplan-Meier analysis. RESULTS: Thirty-one patients had unexpected malignancy and 29 patients (1.6%) had primary lung carcinoma in the explanted lung. Indication for transplantation was chronic obstructive pulmonary disease in 15 patients (48%) and interstitial lung disease for 16 patients (52%). Preoperative imaging showed indeterminate nodules in 10 patients (32%). Pathologic review showed stage I disease in 15 patients (54%), stage II disease in 10 patients (35%), and stage III disease in 2 patients (7%). Recurrence was noted in 8 patients (28%). Most patients had nodal disease (25%) or systemic recurrence (75%). All recurrences occurred within 2 years of the transplantation. For patients with stage I and II disease, freedom from recurrence at 1, 3, and 5 years was 91%, 55%, and 55%, respectively. Overall survival at 1, 3, and 5 years was 78%, 18%, and 14%, respectively. CONCLUSIONS: Most recurrences occur within 2 years after transplantation and are the cause of death in these patients. Patients with nodal disease tend to have higher recurrence rates. Multidisciplinary review of abnormal radiographic findings before transplantation and close follow-up may allow for detection of undiagnosed cancers.

Contemporary Outcomes of Extracorporeal Membrane Oxygenation Used as Bridge to Lung Transplantation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO), when used as bridge to lung transplantation, (BTT) identifies high-risk candidates. Recent advances in cannula design and patient selection fosters "awake ambulatory ECMO" as a viable option for critically ill candidates in an attempt to retard deconditioning while awaiting allografts. METHODS: From 2012 to 2015, 30 patients underwent ECMO as BTT. Candidacy for ECMO was determined before listing for transplant. A dual-lumen single cannula was used first in 13 of 30 patients (43%). Of the remaining 30 patients, 6 (20%) were supported with venoarterial ECMO and 11 (37%) with venovenous ECMO, with double-site cannulation in 11 (37%), and 6 of 11 converted to a dual-lumen single cannula. All ECMO patients were managed in a dedicated heart/lung failure intensive care unit, and early aggressive physical therapy, ambulation, and spontaneous breathing trials were emphasized. RESULTS: BTT was successful in 26 patients (87%). In the 19 patients with dual-lumen single cannula, 5 (26%) were successfully ambulated, and 6 (32%) achieved spontaneous ventilation. Median (25th, 75th percentile) lengths of stay in the intensive care unit and hospital were 33 days (20, 46 days) and 56 days (28, 78 days), respectively, and were 20 and 31 days, respectively, in patients successfully ambulated (intensive care unit: p = 0.5; hospital: p = 0.4). Among all patients who received a transplant, 30-day, 1-year, and 3-year survival were 92%, 85%, and 80%, respectively. Among patients undergoing primary transplants, 3-year survival was 91%. CONCLUSIONS: ECMO as BTT has led to encouraging perioperative outcomes and early survival. Careful patient selection and early use of ECMO seems to allow for preservation of vitality while these critically ill candidates await donor organs, which may improve outcomes.

The incorporated aortomitral homograft for double-valve endocarditis: the 'hemi-Commando' procedure. Early and mid-term outcomes.

OBJECTIVES: Surgical management of invasive double-valve infective endocarditis (IE) involving the intervalvular fibrosa (IVF) is a technical challenge that requires extensive debridement followed by complex reconstruction. In this study, we present the early and mid-term outcomes of the hemi-Commando procedure and aortic root replacement with reconstruction of IVF using an aortomitral allograft. METHODS: From 2010 to 2017, 37 patients with IE involving the IVF underwent the hemi-Commando procedure. Postoperative clinical data and echocardiograms were reviewed for the assessment of cardiac structural integrity and clinical outcomes. RESULTS: Twenty-nine (78%) cases were redo surgery and 15 (41%) were emergency surgery. Preoperatively, 70% (n = 26) of patients were admitted to the intensive care unit and 11% (n = 4) of patients were in septic shock. Ten (27%) patients had native aortic valve IE, while 27 (73%) patients had prosthetic valve IE. Hospital death occurred in 8% (n = 3) of patients due to multisystem organ failure. Postoperative echocardiogram showed no aortic regurgitation in 86% (n = 32) and mild regurgitation in 14% (n = 5) of patients, while mitral regurgitation prevalence was none/trivial in 62% (n = 23), mild in 32% (n = 12) and moderate in 5%. Intact IVF reconstruction was confirmed in all patients with no abnormal communication between the left heart chambers. One-year survival was 91%, while 3-year survival was 82%. Mid-term follow up revealed 1 death secondary to recurrent IE. CONCLUSIONS: Compared to double-valve replacement with IVF reconstruction ('Commando operation'), the early and mid-term outcomes of the hemi-Commando procedure proved to be a feasible treatment option for IVF reconstruction, enabling preservation of the mitral valve and the subvalvular apparatus in high-risk patients with invasive double-valve IE.

Using a novel wireless system for monitoring patients after the atrial fibrillation ablation procedure: the iTransmit study.

BACKGROUND: A novel technology incorporates electrodes into an iPhone case that records an electrocardiographic tracing. OBJECTIVES: The objectives of this study were to examine the feasibility and efficacy of this technology to monitor patients after the atrial fibrillation (AF) ablation procedure and to assess patients' feedback on its ease of use. METHODS: Patients with AF undergoing ablation who had iPhones were screened for enrollment. They were provided with an AliveCor heart monitor (AHM) case and a traditional transtelephonic monitor (TTM). Patients were asked to record their rhythm using both monitors simultaneously whenever they had symptoms or at least once a week. AHM recordings were sent to a secure e-mail account, and TTM recordings were transmitted to our Holter laboratory using landlines. All AHM recordings were reviewed by 1 of 2 blinded electrophysiologists. TTM recordings were reviewed by the primary electrophysiologist. The κ coefficient was calculated to assess agreement between AHM and TTM recordings. Sensitivity and specificity for the detection of AF and atrial flutter with the AHM compared to the TTM were calculated. RESULTS: Sixty patients were enrolled (mean age 60 ± 12 years), and 55 completed the study. There were 389 simultaneous AHM and TTM recordings. The κ statistic was 0.82, indicating excellent agreement between AHM and TTM recordings. If we consider AF and atrial flutter as one diseased state, the AHM had 100% sensitivity and 97% specificity for the detection of AF and atrial flutter. Only 2% of patients found it difficult to use the AHM, and the large majority (92%) preferred to use the AHM to monitor their AF as opposed to the TTM. CONCLUSION: The AHM is an alternative method for monitoring patients with AF after the ablation procedure. Most patients found it easy to use.

Pharmaceutical impurities: regulatory perspective for Abbreviated New Drug Applications.

Impurities in drug substances and drug products have been important regulatory issues in the Office of Generic Drugs by having significant impact on the approvability of Abbreviated New Drug Application (ANDAs). This review begins with a discussion of ANDAs and its similarity/differences with NDAs, highlighting the importance of control of pharmaceutical impurities in generic drug product development and regulatory assessment. An overview of the FDA draft guidance documents "ANDAs: Impurities in Drug Substances" and "ANDAs: Impurities in Drug Products" are provided. This introduces the identification and qualification procedures for ANDAs and approaches to the establishment of acceptance criteria for both drug substance and drug product. Case studies included in this review illustrate the proposed pathway for determination of impurities and their acceptance criteria, based upon the general principles of these guidances.