Is 300 Seconds ACT Safe and Efficient during MiECC Procedures?

INTRODUCTION: The recommended minimum activated clotting time (ACT) level for cardiopulmonary bypass (CPB) of 480 seconds originated from investigations with bubble oxygenators and uncoated extracorporeal circulation (ECC) systems. Modern minimal invasive ECC (MiECC) systems are completely closed circuits containing a membrane oxygenator and a tip-to-tip surface coating. We hypothesized that surface coating and the "closed-loop" design allow the MiECC to safely run with lower ACT levels and that an ACT level of 300 seconds can be safely applied without thromboembolic complications. The aim of this study was to investigate the potential risks during application of reduced heparin levels in patients undergoing coronary surgery. METHODS: In this study, 68 patients undergoing coronary artery bypass grafting with MiECC were randomized to either the study group with an ACT target of 300 seconds or the control group with an ACT of 450 seconds. All other factors of MiECC remained unchanged. RESULTS: The study group received significantly less heparin and protamine (heparin [international units] median [min-max], Red_AC: 32,800 [23,000-51,500] vs. Full_AC: 50,000 [35,000-65,000] p < 0.001; protamine [international units], Red_AC: 18,000 [10,000-35,000] vs. Full_AC: 30,000 [20,000-45,000] p < 0.001). The ACT in the study group was significantly lower at the start of MiECC (mean ± standard deviation: study group 400 ± 112 vs. control group 633 ± 177; p < 0.0001). Before termination of CPB the ACT levels were: study group 344 ± 60 versus control group 506 ± 80. In both groups, the values of the endogenous thrombin potential (ETP) decreased simultaneously. None of the study participants experienced thromboembolic complications. CONCLUSION: Since no evidence of increased thrombin formation (ETP) was found from a laboratory standpoint, we concluded that the use of MiECC with a reduced anticoagulation strategy seems possible. This alternative anticoagulation strategy leads to significant reduction in dosages of both heparin and protamine. We can confidently move forward with investigating this anticoagulation concept. However, to establish clinical safety of ACT below 300 seconds, we need larger clinical studies.

Shed-blood-separation and cell-saver: an integral Part of MiECC? Shed-blood-separation and its influence on the perioperative inflammatory response during coronary revascularization with minimal invasive extracorporeal circulation systems - a randomized controlled trial.

OBJECTIVE: The postoperative systemic inflammatory response after cardiopulmonary bypass (CPB) is still an undesirable side-effect after cardiac surgery. It is most likely caused by blood contact with foreign surfaces and by the surgical trauma itself. However, the recirculation of activated shed mediastinal blood is another main cause of blood cell activation and cytokine release. Minimal invasive extracorporeal circulation (MiECC) comprises a completely closed circuit, coated surfaces and the separation of suction blood. We hypothesized that MiECC, with separated cell saved blood, would induce less of a systemic inflammatory response than MiECC with no cell-saver. The aim of this study was, therefore, to investigate the impact of cell washing shed blood from the operating field versus direct return to the ECC on the biomarkers for systemic inflammation. MATERIAL AND METHODS: In the study, patients with MiECC and cell-saver were compared with the control group, patients with MiECC and direct re-transfusion of the drawn blood shed from the surgical field. RESULTS: High amounts of TNF-α (+ 120% compared to serum blood) were found in the shed blood itself, but a significant reduction was demonstrated with the use of a cell-saver (TNF-α ng/l post-ECC 10 min: 9.5±3.5 vs. 19.7±14.5, p<0.0001). The values for procalcitonin were not significantly increased in the control group (6h: 1.07±3.4 vs. 2.15±9.55, p=0.19) and lower for C-reactive protein (CRP) (24h: 147.1±64.0 vs.134.4±52.4 p=0.28). CONCLUSION: The use of a cell-saver and the processing of shed blood as an integral part of MiECC significantly reduces the systemic cytokine load. We, therefore, recommend the integration of cell-saving devices in MiECC to reduce the perioperative inflammatory response.

Assessment of tenderness of aged bovine gluteus medius muscles using Raman spectroscopy.

A portable 671 nm Raman system was evaluated as a rapid and non-destructive device for the assessment of beef tenderness using 175 gluteus medius muscles (99 for calibration, 76 for validation) aged at -1 °C and 7 °C for fourteen days. Raman and shear force (SF) measurements were performed with the aged beef. The samples stored at -1 °C showed on average only slightly increased SF values. The correlation of Raman spectra with SF using partial least squares regression yielded cross-validated predictions of SF for both storage temperatures with coefficients of determination R(2)cv=0.33-0.79. Validation with independent samples resulted in predictions with R(2)val=0.33. Using thresholds between 30 and 49N, tough and tender samples could be discriminated with partial least squares discriminant analysis with 70-88% and 59-80% accuracy during cross-validation and validation, respectively. These results demonstrate the principle feasibility to predict the SF and thus toughness of raw, aged gluteus beef cuts with a portable Raman device showing potential for grading beef cuts.

State-of-the-art anterior cruciate ligament tears: A primer for primary care physicians.

The purpose of this article is to provide primary care physicians and other members of the medical community with an updated, general review on the subject of anterior cruciate ligament (ACL) tears. We aim to enhance awareness of these injuries and to prepare those practicing in the primary care setting to address these injuries. Because ACL injuries are quite common, it is very likely that a primary care physician will encounter these injuries and need to address them acutely. The current literature is replete with new concepts and controversies regarding ACL injuries, and this article provides a concise review for our target audience in regard to the care of a patient with an ACL injury. This article is composed of an overview with current epidemiologic data, basic anatomy and physiology, clinical presentation, physical examination findings, imaging modalities, and treatment options. After reading this short article, a medical care provider should understand ACL injuries and their appropriate management.

Use of a squatting movement as a clinical marker of function after total knee arthroplasty.

OBJECTIVE: The aims of this study were to evaluate weight bearing during standing and 30- and 60-degree squats approximately 1 wk and 2 mos after surgery and determine whether weight bearing during squatting could be a better clinical marker than standing for identifying perceived functional limitation approximately 1 wk after surgery. A further objective was to determine whether age, body mass index, and number of outpatient visits over the course of rehabilitation predicted weight bearing during a squat approximately 2 mos after surgery. DESIGN: The percentage of body weight placed over both limbs during stand and 30- and 60-degree squats in 38 patients (25 women and 13 men) who had primary unilateral knee arthroplasty was determined. An asymmetry index would be used as a marker that could discriminate between those who perceived at least moderate difficulty with functional tasks and those who perceived only slight or no difficulty with functional activities based on the physical function dimension of the Western Ontario McMaster Universities Osteoarthritis index approximately 1 wk after surgery. Stepwise regression was conducted to determine whether clinical characteristics predicted weight-bearing asymmetry at discharge. RESULTS: At initial visit (first observation), and compared with the uninvolved side, individuals placed significantly less body weight over the involved or operated limb for stand and 30- and 60-degree squats (P < 0.0001). Results were similar at last rehabilitation visit (second observation). Identifying at least moderate self-reported difficulty with functional tasks based on the receiver operator characteristic curve for the asymmetry index for the stand position was 0.64, whereas for the 30- and 60-degree squats, the area under the curve was 0.81 and 0.89, respectively. At discharge from rehabilitation, there was a moderate to good direct relationship (r = 0.70) between the number of rehabilitation visits completed and the weight-bearing asymmetry index for the 60-degree squat. CONCLUSIONS: On the first outpatient visit, individuals who had primary unilateral knee arthroplasty placed more body weight over the uninvolved side for the three weight-bearing positions. With high probability, the asymmetry index for both squatting angles identified perceived functional difficulty. As rehabilitation visits increased, there was a direct association to improved interlimb weight-bearing symmetry when squatting to 60 degrees.

Squatting after primary unilateral total knee arthroplasty: a pilot study examining differences between genders.

OBJECTIVE: To compare the weight bearing of men and women during standing and squatting after knee replacement surgery for osteoarthritis. DESIGN: Two-group, single-surgeon study with patients selected consecutively through a sample of convenience. Patients evaluated at first outpatient rehabilitation visit and at discharge from outpatient services. SETTING: Outpatient orthopedic institute. PARTICIPANTS: Seventeen women (average age, 71 years) and 16 men (69 years) who underwent primary unilateral knee replacement for osteoarthritis. MAIN OUTCOME MEASUREMENTS: Percentage of body weight placed over the surgical limb during standing and during 30° and 60° squats. RESULTS: The men placed a greater percentage of body weight over the surgical limb during the 30° and 60° squats, both at the initial visit and at discharge. Both women and men had similar improvements with all dependent measurements. CONCLUSION: The magnitude of change for women and men was similar, yet percentage of body weight placed over the surgical limb in women was less than in men at the initial visit and did not match that in their male counterparts by discharge.

Closed-chain exercise after simultaneous bilateral knee replacement surgery: a case report.

The purpose of this case report was to present a method for assessing entire lower extremity performance and describe a Medical Exercise Therapy (MET) training program early after simultaneous bilateral total knee replacement (TKR). We also documented perceived function, mobility, and weight-bearing ability during functional tasks. The patient was a 50-year-old male who underwent a simultaneous bilateral procedure and began physical therapy (PT) 16 days postsurgery. Lower extremity performance (weight, repetitions, and load*volume) was assessed weekly using a one-legged horizontal press. Perceived physical abilities, mobility, and body weight placed over each limb during a sit to stand and a squat at two different flexion angles were assessed. At discharge load*volume for the weakest limb was 87% of the strongest side. At discharge, sit-to-stand, and 30 and 60 degree squat asymmetry ranged from 4% to 6%. Perceived abilities and mobility improved from initial visit to discharge. The patient was able to tolerate the closed-chain assessment of lower extremity performance and MET training program early after surgery. The patient made improvements in all functional tests and more importantly maintained a fairly equal distribution of body weight over both limbs during functional activities.

Delaying knee replacement and implications on early postoperative outcomes: a pilot study.

The goal of this study was to compare outcomes during postoperative rehabilitation between individuals who delayed surgery to those who did not delay surgery. Forty-two patients who underwent unilateral total knee replacement (TKR) were categorized into 2 groups: early surgical (n=30, surgery 324 days prior) and late surgical (n=12, surgery >or=325 days from the initial orthopedic office visit). The KSKS, KSFS, SF-12 PC summary, and AROM for knee extension and flexion were assessed preoperatively. The WOMAC, weight bearing during a 30 degrees (SQ30) and 60 degrees (SQ60) squat, and the Timed Up and Go were assessed at the initial visit and discharge of rehabilitation. A Mann-Whitney was used to assess for differences between groups for the WOMAC pain and physical function dimensions at the initial visit and at discharge. A 2x2 ANOVA was used to assess for differences between groups at the initial visit and at discharge for SQ30, SQ60, and Timed Up and Go. Independent t tests were used to assess for differences between groups for clinical measures taken preoperatively. Effect sizes were calculated over postoperative rehabilitation. Regardless of time, the late surgical group placed significantly less body weight on the involved side during SQ30 and took longer to complete the Timed UP and Go. The late surgical group reported greater pain at the initial visit and greater difficulty with functional activities at the initial visit and discharge. Change scores were similar in both groups and effect sizes were moderate to high. Individuals who delayed surgery, for whatever reason, did not perform at levels of their counterparts who had shorter waiting times.

Minimal extracorporeal circulation and off-pump compared to conventional cardiopulmonary bypass in coronary surgery.

OBJECTIVES: Although minimal extracorporeal circulation (MECC) and off-pump surgery are equal or better alternatives to conventional cardiopulmonary bypass (CCPB) regarding perioperative morbidity, use of blood and blood products and completeness of revascularization, CCPB is still being used in the majority of coronary artery bypass grafting (CABG) operations. METHODS AND RESULTS: We investigated 1472 CABG operations in our center. A total of 1143 CABG operations were performed using CCPB, 220 using MECC and 109 were performed as off-pump coronary artery bypass (OPCAB). All patients were recorded prospectively. Perioperative follow-up was focused on the occurrence of arrhythmia, neurocognitive disorders and the need of blood and blood products. Operative mortality rates were comparable in all three groups. The mean number of distal anastomoses was 3.2+/-0.6 in the MECC group, 3.4+/-0.7 in the CCPB group and 1.9+/-0.8 in the OPCAB group (P=0.01). Arrhythmia occurred in 25% of the MECC group and in 35.6% of the CCPB group (P=0.05). Arrhythmia occurred in 21.7% of the OPCAB group. Seven patients (3%) of the MECC group suffered neurocognitive disorders perioperatively compared to 74 (7%) patients of the CCPB group (P=0.05) and three patients of the OPCAB group (3%). The median number of blood transfusions per patient was 0.8 in the MECC group, 1.8 in the CCPB group and 0.8 in the OPCAB group (P<0.0001). CONCLUSIONS: Perioperative morbidity of MECC and OPCAB is comparable to or even less in comparison to CCPB. MECC allows CABG surgery in cardiac arrest so that completeness of revascularization is being warranted and longer patency rates can be guaranteed. Furthermore, the use of blood and blood products is significantly less in MECC surgery so that MECC should be considered first choice in CABG surgery over CCPB and OPCAB.

Expression of serologically identified tumor antigens in acute leukemias.

Cancer/testis antigens (CTA) are an expanding family of immunogenic proteins selectively expressed in human neoplasms. As little is known about the expression of serologically identified CTA in leukemias so far, we investigated the expression of 5 CT genes (SSX-1, HOM-MEL-40/SSX-2, HOM-TES-14/SCP-1, SCP-3 and NY-ESO-1) in leukemic blood samples obtained from patients with either acute lymphatic leukemias (ALL) or myelocytic leukemia (AML). RT-PCR-analyses showed no expression of any of the CT-genes in the leukemia samples of 19 patients with AML, whereas frequent expression was found in ALL. In the 17 ALL cases studied, SCP3a, SSX-1, HOM-MEL-40/SXX-2 and HOM-TES-14/SCP-1 were expressed in 47, 29, 29 and 12%, respectively, whereas no case was positive for NY-ESO-1. 65% of patients with ALL showed expression of at least one, 41% of two or more of the five CT-genes investigated. We conclude that a majority of the ALLs might be amenable for specific immunotherapeutic interventions. However, the identification of additional antigens with a frequent expression in leukemias is warranted to allow the development of widely applicable polyvalent leukemia vaccines.

A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing.

We describe here the definition and characterization of antigen CT-8/HOM-TES-85 encoded by a previously unknown gene and identified by serological expression screening using antibodies from a seminoma patient. Intriguingly, the leucine zipper region of CT-8/HOM-TES-85 shows an atypical amphipathy with clusters of hydrophobic residues that is exclusively shared by the N-myc proto-oncogene. CT-8/HOM-TES-85 gene is tightly silenced in normal tissues except for testis. However, it is frequently activated in human neoplasms of different types including lung cancer, ovarian cancer, melanoma and glioma. Endogenous as well as heterogeneously expressed CT-8/HOM-TES-85 targets predominantly to the nucleus forming a distinctive speckled pattern of nuclear dots arranged in macromolecular structures. By co-localization studies these speckles were identified as loci of transcriptional activity and splicing, suggesting that CT-8/HOM-TES-85 may be involved in these processes. The aberrant expression of CT-8/HOM-TES-85 in human neoplasms might therefore be involved in cancer associated alterations of transcriptional or post-transcriptional processes and thus may disclose new mechanisms involved in the manifestation of the cancer phenotype.