Chronic lung allograft dysfunction subtype analysis by computed tomography volumetry.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation. Of the two subtypes, restrictive allograft syndrome (RAS) is characterized by a larger lung volume decrease and worse prognosis than bronchiolitis obliterans syndrome (BOS). We used computed tomography (CT) volumetry to classify CLAD subtypes and determined their clinical impact. METHODS: Adult primary lung transplants performed 2003-2015 (n = 167) were retrospectively evaluated for CLAD and subclassified with CT volumetry. Lung volume decrease of < 15% from baseline resulted in BOSCT-vol and ≥15% resulted in RASCT-vol diagnosis. Clinical impact of CLAD subtypes was defined, and the prognostic value of different lung function, radiological, and lung volume parameters present at the time of CLAD diagnosis were compared. RESULTS: CLAD affected 43% of patients and was classified with CT volumetry as BOSCT-vol in 89% and RASCT-vol in 11%. Median graft survival estimate in RASCT-vol was significantly decreased compared to BOSCT-vol (1.6 vs. 9.7 years, P = .038). At CLAD onset, RASCT-vol diagnosis (P = .05), increased lung density (P = .007), and more severe FEV1 (P = .004) decline from baseline, increased graft loss risk in multivariate analysis. CONCLUSIONS: CT volumetry serves to identify lung transplant patients with a poor clinical outcome but should be validated in prospective trials.

Unilateral pulmonary oedema after minimally invasive and robotically assisted mitral valve surgery.

OBJECTIVES: Unilateral pulmonary oedema (UPO) is a severe complication of minimally invasive cardiac surgery. UPO rates and UPO-related mortality vary considerably between different studies. Due to lack of consistent diagnostic criteria for UPO, the aim of this study was to create a reproducible radiological classification for UPO. Also, risk factors for UPO after robotic and minimally invasive mitral valve operations were evaluated. METHODS: Two hundred and thirty-one patients who underwent elective minimally invasive mitral valve surgery between January 2009 and March 2017 were evaluated. Chest radiographs of the first postoperative morning were categorized into 3 UPO grades based on the severity of radiological signs of pulmonary oedema described in this study. The radiographs were analysed by 2 independent radiologists and interobserver agreement was evaluated. The clinical significance of the classification was evaluated by comparing postoperative PaO2/FiO2 values and total ventilation times between the different UPO grades. Also, multivariable logistic regression analysis was employed to identify risk factors for UPO. RESULTS: Interobserver agreement was substantial (Kappa = 0.780). Median total ventilation times were significantly longer with increasing severity of UPO, 15 (interquartile range 12-18) h for no UPO, 18 (interquartile range 15-24) h for grade I UPO and 25 (interquartile range 21-31) h for grade II UPO. Pulmonary hypertension [adjusted odds ratios (AOR) 2.51, 95% confidence intervals (CI) 1.43-4.40; P = 0.001], moderate or severe heart failure (AOR 2.88, 95% CI 1.27-6.53; P = 0.011), body mass index (AOR 1.14, 95% CI 1.02-1.28; P = 0.017) and cardiopulmonary bypass time (AOR 1.02, 95% CI 1.01-1.03; P < 0.001) were identified as independent risk factors for UPO and robotic approach (AOR 0.27, 95% CI 0.12-0.62; P = 0.002) as protective against UPO. CONCLUSIONS: Due to the variability of the diagnostic criteria for UPO in previous studies, a radiological classification for UPO is required to reliably assess the rates and risk factors for UPO. The radiological classification described in this study demonstrated high interobserver agreement and correlated with total ventilation times and postoperative PaO2/FiO2 values.

Ingraft chimerism in lung transplantation--a study in a porcine model of obliterative bronchiolitis.

BACKGROUND: Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs. METHODS: A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors. RESULTS: Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (R=0.610-0.671 and p<0.05) and of obliteration of the bronchial lumen (R=0.698 and p<0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (p<0.05), or bronchial wall (p<0.05). CONCLUSIONS: In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.

Long-term survival and quality of life after cardiac resuscitation following coronary artery bypass grafting.

OBJECTIVE: Follow-up studies of patients surviving emergency resternotomy, open cardiac massage, and additional emergency cardiac surgery following coronary artery bypass grafting (CABG) remain sparse and studies focusing on health-related quality of life are lacking. Our aim was to elucidate the long-term course of patients experiencing this hazardous complication. METHODS: Between 1988 and 1999, 76 patients suffered sudden hemodynamic collapse following isolated CABG. All patients underwent emergency resternotomy and open cardiac massage. An emergency cardiac reoperation was performed in the 62 (82%) primary survivors. Additional 76 patients were pair-matched to the study patients on the basis of their preoperative characteristics and served as controls. Of the study patients, 41 (54%), and of the controls, 76, (100%) were discharged. In December 2009, all patients were traced with respect to mortality data and the health-related quality of life of living patients was studied using the RAND-36 Item Health Survey questionnaire. RESULTS: Altogether 19 (73%) of the 26 study patients, and 38 (84%) of the 45 controls were available. After exclusion of the early deaths, the life expectancy was similar between the groups: neither overall (p = 0.60) nor cardiac (p = 0.64) survival differed significantly after a mean follow-up time of 15.1 ± 3.5 years. In addition, cardiac re-interventions were equally frequently required in both the groups. The RAND-36 scores were congruent (p = ns) between the groups and the age- and sex-matched national reference population in the health-related quality-of-life dimensions describing physical, mental, and social domains. CONCLUSIONS: Patients who have survived severe hemodynamic collapse, open cardiac massage, and emergency cardiac reoperation following CABG achieve similar long-term prognosis in terms of survival and cardiac interventions as the pair-matched control patients. In addition, 15 years postoperatively, they have a good health-related quality of life, similar to that of an age- and sex-matched national reference population.

Increased preoperative thrombin generation and low protein S level associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting.

In a previous study, preoperative levels of activated protein C (APC) were associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting (CABG). Protein C is activated by thrombin. Protein S, the cofactor of activated protein C, has activated protein C-independent anticoagulant activity and cytoprotective effects. Therefore, the objective of this study was to test whether preoperative, baseline levels of either thrombin or protein S were associated with hemodynamic performance or markers of myocardial damage after CABG. One hundred patients undergoing elective on-pump CABG were prospectively studied. Prothrombin fragment F1+2 (a marker of thrombin generation) and free protein S were measured preoperatively and cardiac index, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) were measured serially thereafter at fixed time points. Cardiac biomarkers CK-MBm and TnT were measured postoperatively. There was an inverse correlation between preoperative F1+2 and free protein S levels (r= -0.30, p=0.003). High preoperative F1+2 and low preoperative protein S levels were associated with a less favorable hemodynamic profile postoperatively. Patients with F1+2 in the highest decile (≥0.85 nmol/l) and patients with preoperative protein S in the lowest decile (≤63%) had lower CI values, and higher pulmonary and systemic vascular resistance index values postoperatively than comparison patients. Preoperative F1+2 or protein S did not correlate with postoperative cardiac biomarker levels. Baseline activation of coagulation and the balance between pro-coagulant and anti-coagulant factors preoperatively might have implications for postoperative hemodynamic recovery after CABG.

Medico-legal autopsy in postoperative hemodynamic collapse following coronary artery bypass surgery.

Sudden unexpected postoperative hemodynamic collapse with a high mortality develops in 1-3% of patients undergoing coronary artery bypass surgery (CABG). The contribution of surgical graft complications to this serious condition is poorly known and their demonstration at autopsy is a challenging task. Isolated CABG was performed in 8,807 patients during 1988-1999. Of the patients, 76 (0.9%) developed sudden postoperative hemodynamic collapse resulting in subsequent emergency reopening of the median sternotomy and open cardiac massage. Further emergency reoperation could be performed in 62 (82%) whereas 14 patients died prior to reoperation and a further 21 did not survive the reoperation or died a few days later. All 35 (46%) patients who did not survive were subjected to medico-legal autopsy combined with postmortem cast angiography. By combining clinical data with autopsy and angiography data, various types of graft complications were observed in 27 (36%, 1.3 per patient) of the 76 patients with hemodynamic collapse. There were no significant differences in the frequency (33 vs. 40%) or number of complicated grafts per patient (1.2 vs. 1.4) between those who survived reoperation and who did not. Autopsy detected 25 major and minor findings not diagnosed clinically. Postmortem cast angiography visualized 2 graft twists not possible to detect by autopsy dissection only. Surgical graft complications were the most frequent single cause for sudden postoperative hemodynamic collapse in CABG patients leading to a fatal outcome in almost half of the cases. Postmortem angiography improved the accuracy of autopsy diagnostics of graft complications.

Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery.

BACKGROUND AND AIMS: The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer's acetate on cardiac and stroke volume index after cardiac surgery. MATERIAL AND METHODS: Three consecutive boluses (each 7 mL·kg(-1)) of either 6% HES 130/0.4, 4% gelatine, or Ringer's acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg(-1)) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg(-1). RESULTS AND CONCLUSION: Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min(-1)·m(-2) (0.7), 34.1 (6.7) ml·m( -2)] than in the gelatine group [2.2 L·min(-1)·m( -2) (0.6), 25.8 (7.2) ml·m(-2)] after completion of 7 mL·kg(-1) of study solution. At this stage, the effect of gelatine did not differ from Ringer's acetate. After completion of 14 mL·kg(-1) and 21 mL·kg(-1) of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer's acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer's acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer's acetate group.