Arthroscopic partial meniscectomy versus placebo surgery for a degenerative meniscus tear: a 2-year follow-up of the randomised controlled trial.

OBJECTIVE: To assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus. METHODS: In this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35-65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out. RESULTS: In the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, -4.3; 95% CI, -11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (-3.2; -8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (-0.4; -1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups. CONCLUSIONS: In this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.

Small-scale slow glucose feed cultivation of Pichia pastoris without repression of AOX1 promoter: towards high throughput cultivations.

Recombinant protein synthesis in Pichia pastoris is generally controlled by the strong methanol inducible AOX1 promoter which is repressed by glucose and glycerol. In shake flasks, commonly one or two methanol pulses are added per day for induction. Such pulse feeding procedure leads to carbon starvation phases, which may enhance proteolytic activities and, therefore, cause product losses. Starvation between the methanol pulses could be avoided with a continuous enzymatic feed of glucose from a glucose-based polymer. The amount of glucose was low enough to prevent AOX1 repression by glucose. Energy and carbon were continuously supplied for cell maintenance resulting in significantly increased cell densities and product activities, as shown here at the example of a fungal lipase expressed in P. pastoris. A threefold improvement in measured product activity was obtained by applying enzymatic glucose feed and a further improvement was achieved by applying a defined mixture of ammonium compounds. The strategy described here simplifies the general procedure in shaken cultures by allowing the direct continuation of the cultivation from glucose to the methanol-based production phase without a medium change. It is easily applicable to multiwell plates and thus beneficial for high throughput applications.

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.

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.

Predictive factors of hemodynamic collapse after coronary artery bypass grafting: a case-control study.

OBJECTIVE: Sudden hemodynamic collapse after coronary artery bypass graft (CABG) surgery is a complication with high morbidity and mortality. The aim of this study was to explore factors possibly predictive of this major complication. DESIGN: Retrospective case-control study. SETTING: University hospital, department of cardiothoracic surgery. PARTICIPANTS: Between 1988 and 1999, of 8,807 CABG patients, a total of 76 (0.9%) suffered hemodynamic collapse after CABG surgery unrelated to pericardial tamponade or bleeding. Preoperatively matched patients (by age, sex, New York Heart Association classification, number of diseased vessels, left ventricular ejection fraction, and diabetes) served as a control group (n = 76). INTERVENTIONS: Patients with sudden cardiovascular collapse underwent emergency reopening of the sternotomy and open cardiac massage (OCM group). Several pre-, intra-, and postoperative variables were compared, and significant parameters in match-pair analysis were further tested with regression techniques. MEASUREMENTS AND MAIN RESULTS: Of the 76 OCMs, 57 (75%) occurred during the first 5 postoperative hours. In-hospital mortality was 46% (35 of 76) versus 0% in controls; 5-year survival was 49% versus 95%. In the OCM group, cardiopulmonary bypass (CPB) time was significantly prolonged (p = 0.0024), and cardiac index (p = 0.05) and the first acid-base values after CPB were lower (pH, p = 0.0057; BE, p = 0.0014). Postoperative myocardial ischemia appeared in 33% of patients in the OCM group and in 8% of controls (p < 0.0001). OCM-group patients more frequently required postoperative inotropic (epinephrine, p = 0.0002) and mechanical support (intra-aortic balloon pump, p = 0.005). Regression analysis revealed a correlation between cardiopulmonary resuscitation risk and low cardiac index, postoperative ischemia, and low pH level. CONCLUSION: Inadequate tissue perfusion, postoperative myocardial ischemia, and increased need for inotropic and mechanical support preceded hemodynamic collapse. Interventions to improve tissue perfusion and to prevent and treat myocardial ischemia may result in a more favorable outcome.

N-acetylcysteine as an additive to crystalloid cardioplegia increased oxidative stress capacity in CABG patients.

OBJECTIVE: This prospective, randomized study was designed to assess the effects of N-acetylcysteine (NAC) in coronary artery bypass graft (CABG) patients. DESIGN: Thirty-five consenting CABG patients with normal myocardial function were randomly divided into control (C) patients (N = 20) who received crystalloid (Plegisol) cardioplegia, and NAC patients receiving NAC in a 0.04 mol/l solution (N = 15) in Plegisol. Simultaneous coronary sinus and aortic blood samples, and myocardial biopsies were taken 1, 5 and 10 min after declamping. Hemodynamics was measured invasively for 24 h. RESULTS: There were no adverse effects observed. The myocardial glutathione content was significantly better preserved (p = 0.0001) and myeloperoxidase activity was over two times lower in the NAC group than in the C group (p = 0.03). The trap capacity gradient between the aorta and the coronary sinus increased significantly during the first minute of reperfusion in the treatment group (p = 0.001) when compared with the C group. In the first minute after reperfusion there were more leukocytes sequestered in the coronary circulation (p = 0.04) in the C group. The invasive hemodynamic data did not differ significantly between the groups. The incidence of arrhythmias was equal. CONCLUSION: NAC increased tissue capacity against oxidative stress and decreased inflammatory response in CABG patients with normal ejection fraction.