An Algorithm for Fitting Mixtures of Gompertz Distributions to Censored Survival Data

We consider the fitting of a mixture of two Gompertz distributions to censored survival data. This model is therefore applicable where there are two distinct causes for failure that act in a mutually exclusive manner, and the baseline failure time for each cause follows a Gompertz distribution. For example, in a study of a disease such as breast cancer, suppose that failure corresponds to death, whose cause is attributed either to breast cancer or some other cause. In this example, the mixing proportion for the component of the mixture representing time to death from a cause other than breast cancer may be interpreted to be the cure rate for breast cancer (Gordon,'90a and'90b). This Gompertz mixture model whose components are adjusted multiplicatively to reflect the age of the patient at the origin of the survival time, is fitted by maximum likelihood via the EM algorithm (Dempster, Laird and Rubin,'77). There is the provision to handle the case where the mixing proportions are formulated in terms of a logistic model to depend on a vector of covariates associated with each survival time. The algorithm can also handle the case where there is only one cause of failure, but which may happen at infinity for some patients with a nonzero probability (Farewell,'82).

Cardiac transplant coronary artery disease: A multivariable analysis of pretransplantation risk factors for disease development and morbid events

AbstractCoronary artery disease after cardiac transplantation is a major obstacle to long-term survival. The development and progression of coronary artery disease after cardiac transplantation was analyzed in 217 consecutive patients undergoing transplantation. The actuarial freedom from any coronary artery disease (by angiography or autopsy) was 81% at 2 years and 20% at 8 years after transplantation. Coronary artery disease was more prevalent in male than female patients (30% versus 50% free of coronary artery disease at 5 years, p = 0.01). By multivariable analysis, pretransplantation risk factors identified for coronary artery disease included pretransplantation positive cytomegalovirus serologic status of the recipient ( p = 0.002) and older donor age (p = 0.07). Progression of coronary artery disease was variable in both time of onset and rate. Earlier detection did not result in more rapid progression. Coronary events severe enough for retransplantation ( n = 8) and/or death from coronary artery disease ( n = 9) occurred in 15 patients, of whom four underwent retransplantation. The actuarial freedom from coronary events was 88% at 5 years and 79% at 8 years. By multivariable analysis, only male recipient ( p = 0.05) was a risk factor for coronary events. Seven of the 15 patients (47%) with coronary events died suddenly of coronary artery disease without prior angiographic evidence of severe coronary disease. Coronary artery disease is progressive. Improved surveillance methods are required to detect the disease and institute timely intervention to prevent the occurrence of unanticipated death. (J THORAC CARDIOVASC SURG 1995;109:1081-9

Initial United States experience with the Paracor HeartNet⁎⁎Paracor Medical, Inc, Sunnyvale, Calif. myocardial constraint device for heart failure

ObjectiveThis study was undertaken to review the initial results and surgical safety data for the US Food and Drug Administration safety and feasibility trial of the Paracor HeartNet (Paracor Medical, Inc, Sunnyvale, Calif.) myocardial constraint device.MethodsPatients with New York Heart Association functional class II or III heart failure underwent device implantation (n = 21) through a left minithoracotomy.ResultsThe average age was 53 years (31–72 years). There were 18 men and 3 women, and 17 patients had nonischemic etiology of heart failure. Mean heart failure duration was 8.3 years (1.4-18.8 years). Average ejection fraction was 22% (11%-33%), with an average left ventricular end-diastolic dimension of 74 mm (55-94 mm). Previous medical therapy included angiotensin-converting enzyme inhibitors, β-blockers, diuretics, digoxin, and aldosterone receptor blockers. At implantation, 17 patients had implantable electronic devices: 1 biventricular pacemaker, 11 biventricular pacemakers with cardioverter-defibrillators, and 5 implantable cardioverter-defibrillators. Patient comorbidities included hypertension in 10 cases, diabetes mellitus in 8, myocardial infarction in 1, and ventricular tachycardia in 8. Mean operative time was 68 minutes (42–102 minutes), and implantation time averaged 15 minutes (5–51 minutes). The average time to ambulation was 1.6 days (1–4 days). The intensive care unit stay averaged 3.3 days (1–16 days), and hospital stay averaged 6.3 days (4–16 days). Atrial fibrillation occurred in 2 patients, and there were 2 in-hospital deaths.ConclusionsThe Paracor device can be implanted in patients with heart failure and reduced left ventricular function with a high degree of success. Significant surgical complications were infrequent. The initial US experience supports the conduct of a randomized, controlled, pivotal trial

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-021-00425-4

An Algorithm for Fitting Mixtures of Gompertz Distributions to Censored Survival Data

We consider the fitting of a mixture of two Gompertz distributions to censored survival data. This model is therefore applicable where there are two distinct causes for failure that act in a mutually exclusive manner, and the baseline failure time for each cause follows a Gompertz distribution. For example, in a study of a disease such as breast cancer, suppose that failure corresponds to death, whose cause is attributed either to breast cancer or some other cause. In this example, the mixing proportion for the component of the mixture representing time to death from a cause other than breast cancer may be interpreted to be the cure rate for breast cancer (Gordon, 1990a and 1990b). This Gompertz mixture model whose components are adjusted multiplicatively to reflect the age of the patient at the origin of the survival time, is fitted by maximum likelihood via the EM algorithm (Dempster, Laird and Rubin, 1977). There is the provision to handle the case where the mixing proportions are formulated in terms of a logistic model to depend on a vector of covariates associated with each survival time. The algorithm can also handle the case where there is only one cause of failure, but which may happen at infinity for some patients with a nonzero probability (Farewell, 1982)

Nina Braunwald: a female pioneer in cardiac surgery

Nina Starr Braunwald, the first female cardiac surgeon, made headlines during a time when almost all specialty surgeons were men. Women have typically been deterred from entering surgical specialties, in part because of their traditional dual burden of managing their households and careers. Instead, female medical students and junior doctors have tended to be more attracted to medical specialties. This was the reality during Dr. Braunwald's venture into medicine in 1949. However, she never allowed negative ideas to keep her from joining a surgical training program. Under the mentorship of the prominent cardiac surgeons Charles Hufnagel and Andrew Morrow, Dr. Braunwald progressed in her career by conducting research that led to her development and implantation of the first prosthetic mitral valve. She was also a great teacher. Dr. Braunwald balanced her personal and professional activities admirably, and her example still inspires female doctors to consider careers in cardiothoracic surgery. In this report, we provide details of her impact on cardiac surgery and insights into her successes

Pulmonary transplantation for advanced bronchioloalveolar carcinoma

AbstractBackground: No effective therapy is currently available for the diffuse stage of bronchioloalveolar carcinoma. Objective: We tested the hypothesis that total lung replacement with standard lung transplantation techniques would provide curative therapy. Methods: Nine patients aged 31 to 58 years with bronchioloalveolar carcinoma were entered in the study. Five patients initially had bilateral diffuse tumor. Four patients had recurrence in the contralateral lung after pulmonary resection. Results: Between 1993 and 1998, all 9 patients underwent transplantation (2 single-lung and 7 bilateral transplants, 1 reoperative single-lung transplant, and 1 reoperative bilateral transplant). Two patients had mediastinal node metastasis (level 7) at the time of transplantation, and 1 of these had a frankly invasive adenocarcinoma. Of the 8 patients with pure bronchioloalveolar carcinoma, 6 had recurrent pulmonary tumor after transplantation. In 2 of these patients the tumor was localized and could be resected with left lower lobectomy in one case and left pneumonectomy in the other. One is alive 89 months after transplantation; the other died 82 months after transplantation. Four other patients had a diffuse pattern of pulmonary recurrence. Two died of progressive pulmonary failure; 1 of these had retransplantation with recurrence. A third patient died of cerebral edema shortly after bilateral retransplantation. The other patient is alive with recurrence 39 months after transplantation and has bronchiolitis obliterans. Two patients without recurrence are well with unrestricted performance levels 87 and 76 months after transplantation. Conclusions: Transplantation produces a powerful palliative outcome in patients with advanced bronchioloalveolar carcinoma, but the recurrence rate is high. Transplantation for this indication remains controversial.J Thorac Cardiovasc Surg 2003;125:45-