Van N. Michalek

Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias.

Objective:To present the longest follow-up report of any lipid-atherosclerosis intervention trial. Summary of Background Data:The Program on the Surgical Control of the Hyperlipidemias (POSCH), a secondary, clinical/arteriographic, randomized controlled trial, was the first lipid-atherosclerosis trial to demonstrate unequivocally that low density lipoprotein cholesterol reduction reduced the incidence of coronary heart disease death and myocardial infarction. Methods:We report POSCH 25 years follow-up for overall mortality, specific cause of death, and certain subgroup analyses, as well as a prediction for increase in life expectancy derived from the POSCH database, supplemented by the 2006 National Death Index, 1989–2006. Results:There were 838 patients randomized in POSCH (421 surgery, 417 control). At 25 years follow-up, the difference in the restricted mean survival and the logrank (Mantel-Haenszel) statistic was statistically significant, with survival probabilities of 0.57 (surgery) and 0.51 (controls). Cause of death data indicated a significant increase in cardiovascular deaths in the control group; cancer deaths were also greater in the control group but this was not significant. The most compelling subgroup analysis was a significant increase in survival, starting at 5 years after randomization, in the surgery group for patients with an ejection fraction ≥50%, with relative probabilities of 0.61 (surgery) and 0.51 (control). The estimated incremental increase in life expectancy over more than 25 years of follow-up was 1.0 year overall and 1.7 years in the cohort with an ejection fraction ≥50%. Conclusions:A 25-year mortality follow-up in POSCH shows statistically significant gains in overall survival, cardiovascular disease-free survival, and life expectancy in the surgery group compared with the control group.

Gastric plication: preclinical study of durability of serosa-to-serosa apposition

BACKGROUND Vertical gastric plication is a novel surgical approach for reducing the stomach capacity. Anterior surface plication and greater curvature plication are variations of vertical gastric plication that reduce the gastric capacity through infolding of the anterior surface or greater curvature of the stomach, respectively. These approaches have been tested, with positive results in a small number of preclinical and clinical trials. A key step toward greater investigation of vertical gastric plication as a viable bariatric procedure would be confirmation that the apposed serosal tissues can be securely and durably bonded. We compared the short-term durability of gastric plications and serosal bonds using a variety of fastening devices and techniques in a university hospital and private company setting. METHODS A total of 30 anterior surface plication and 8 greater curvature plication procedures were performed using an open or a laparoscopic surgical technique in 38 hound dogs. The fastening devices used were T-tags, buttressed T-tags, 2 types of suture, and 4 types of staple-based fasteners. The density of the fastening devices was varied among the dogs. With 3 exceptions (2 in keeping with the study design and 1 due to complications), the dogs were followed up for 8 weeks. Histologic examinations and tensile testing were performed postmortem. RESULTS All fastening devices created durable plication folds, except for 1 technique. The only technique that did not produce durable serosa-to-serosa adhesions was a staple/suture combination. Intentional abrasion of the apposed sites had no demonstrable effect on the bonds between the tissues in any group. Increasing the fastener density and number of rows increased the adhesions within the folds. CONCLUSION Our findings have confirmed the short-term durability and development of dense fibrous appositions of the serosal folds for fastening approaches that create fixed serosal apposition. Additional studies are needed to identify the optimal fastening modality for anterior surface plication, greater curvature plication, and, ultimately, clinical applications of this procedure.

Effect Of Plasma Cholesterol On Red Blood Cell Oxygen Transport

1. Oxygen (O2) transfer from the blood to tissues is a function of the red blood cell (RBC) O2 saturation (SO2), the plasma O2 content being negligible. Under conditions of increased tissue O2 demand, the SO2 of arterial blood does not change appreciably (97%); however, the SO2 of mixed venous blood, equal to that of the perfused tissues, can go as low as 20%.

Plasma cholesterol: an influencing factor in red blood cell oxygen release and cellular oxygen availability.

BACKGROUND A fairly immediate reduction in angina pectoris symptoms after cholesterol lowering has been described. Our previous findings in rabbits and in a four-patient human pilot study indicated the existence of an RBC membrane barrier to oxygen (O2) transport in the presence of hypercholesterolemia. Our current objective was to determine whether, and to what extent, the plasma cholesterol concentration is an influencing factor in RBC O2 release and cellular O2 availability. STUDY DESIGN In an unique O2 diffusion analysis system, blood samples from 100 patients referred for lipid modification were analyzed. After 1 to 2 minutes of mixing in our diffusion analysis system, the next 1 to 2 minutes of circulation is comparable with 1 to 2 seconds of myocardial capillary flow. RBC O2 diffusion was defined by the depletion rate of total O2 content in blood from full O2 saturation (98%) to desaturation (approximately 60%). Relative tissue O2 availability was defined as the percentage decrease in O2 availability between the high-cholesterol group and the low-cholesterol group. RESULTS The 100 patients were divided almost equally into two groups on the basis of plasma cholesterol ranges of 175 to 229 mg/dL (n=49) and 230 to 299 mg/dL (n = 51). The mean cholesterol concentrations and percentage increases in the high-cholesterol group over the low-cholesterol group were: for plasma, 206 +/- 0.3 and 256 +/- 0.4 mg/dL, 24.3% (p < 0.001); for RBCs, 93 +/- 0.2 and 106 +/- 0.2mg/dL, 14.0% (p < 0.001); and for RBC membranes, 41 +/- 0.1 and 54 +/- 0.2mg/dL, 31.7% (p < 0.001). The blood O2 diffusion curves were distinctly different between the high- and the low-cholesterol groups (p < 0.05). Blood O2 diffusion, defined by the blood O2 diffusion curves, was inversely proportional to the plasma, RBC, and RBC-membrane cholesterol concentrations. The relative tissue O2 availability, after a circulation period of more than 3 minutes in the diffusion system, showed a decrease of 17.5% (p < 0.05) between the plasma cholesterol groups. In comparing the two plasma cholesterol concentration extremes of less than 200mg/dL (n= 14) and greater than 275 mg/dL (n= 11) after a circulation period of more than 3 minutes in the diffusion system, we found a decrease in relative tissue O2 availability of 35.8% (p < 0.05). CONCLUSIONS The plasma cholesterol concentration may be an influencing factor in RBC-membrane cholesterol content, which, in turn, may regulate RBC-membrane O2 transport, RBC O2 release, and cellular O2 availability. The implications of this work include the addition of angina pectoris control to the indications for appropriate lipid modification and the development of an in vitro blood stress test to replace patient cardiac stress testing.

Effects on GLP-1, PYY, and leptin by direct stimulation of terminal ileum and cecum in humans: implications for ileal transposition☆

BACKGROUND We do not have a unified, scientifically tested theory of causation for obesity and its co-morbidities, nor do we have explanations for the mechanics of the metabolic/bariatric surgery procedures. Integral to proffered hypotheses are the actions of the hormones glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and leptin. The objective of this study was to obtain blood levels of GLP-1, PYY, and leptin after stimulation of the terminal ileum and cecum by a static infusion of a food hydrolysate in morbidly obese patients undergoing a duodenal switch procedure. SETTING University Hospital. METHODS Plasma levels of GLP-1, PYY, and leptin were obtained at 0, 30, 60, 90, and 120 minutes after instillation of 240 mL of a food hydrolysate into the ileum or cecum. RESULTS The mean±SD GLP-1 values by cecal stimulation for 0, 30, 60, 90, and 120 minutes were: 41.3±23.2; 39.6±21.8; 38.9±19.1; 47.4±22.3; 51.7±27.3 pM, and by ileal stimulation: 55.0±32.8; 83.4±16.1; 78.7±23.8; 84.7±23.5; 76.4±25.6. The mean±SD PYY values by cecal stimulation were: 62.1±24.8; 91.1±32.8; 102.1±39.6; 119.6±37.5; 130.3±36.7, and by ileal stimulation: 73.8±41.6; 138.1±17.7; 149.5±23.3; 165.7±24.3; 155.5±29.1. Percent change in PYY levels increased ~150%, GLP-1 increased ~50%, and leptin decreased ~20%. CONCLUSION Direct stimulation of the human terminal ileum and cecum by a food hydrolysate elicits significant plasma GLP-1 and PYY elevations and leptin decreases, peaking at 90-120 minutes. The ileal GLP-1 and PYY responses exceed those of the cecum, and the PYY effect is about 3-fold that of GLP-1. The results of this study question the satiety premise for ileal transposition.

Pilot study of oxygen transport rate of banked red blood cells

Background and Objectives  Dynamic oximetry provides a new way to assess the effect of blood storage on the oxygen transport rate (OTR).

Micro-orifice metabolic/bariatric surgery under IV sedation/local anesthesia: porcine feasibility study.

BackgroundAs the volume and scope of metabolic/bariatric surgery increases, there is a definite trend toward the development and utilization of simpler and safer procedures. The laparoscopic approach has certain disadvantages that can be avoided by a technique for abdominal access via a micro-orifice incision under intravenous (IV) sedation/local anesthesia, without general anesthesia, insufflation, and intubation.MethodsIn a porcine model, we used the implantation of the TANTALUSTM System as a prototype for the micro-orifice, IV sedation/local anesthesia approach. The study was conducted in five ex vivo stomachs, four cadavers, and six in vivo animals, the last four of which underwent surgery under IV sedation/local anesthesia.ResultsAccurate implantation of electrodes was achieved in all ex vivo, cadaver, and in vivo preparations with no mucosal penetration, confirmed by examination of the open porcine stomachs. Operative time in this learning setting was 1 h 43 min in the last three operated animals. Feasibility was established for using the single incision to tunnel and construct subcutaneous pockets for the pulse generator and the charge coil. No major operative or postoperative complications occurred.ConclusionsUsing the TANTALUSTM System as a metabolic/bariatric surgery prototype model, this study successfully tested the feasibility of micro-orifice surgery, under IV sedation/local anesthesia. This study will be followed by human trials that may offer an alternative approach for the performance of metabolic/bariatric surgery.

A novel device for measuring the effect of cholesterol on the release of oxygen from red blood cells

A novel method has been devised to measure the effect of cholesterol on the release of oxygen (O/sub 2/) from the red blood cell (RBC) into a tailored environment, which can be made to mimic myocardial tissue. Cholesterol affects the cell membrane of RBCs and thus the release of O/sub 2/ into tissue. While this is true of all tissue, the myocardium is especially sensitive because of its critical nature, high O/sub 2/ requirements, and the shortness of time that arterial blood spends in the muscle. Calculations are presented that show that the release time for O/sub 2/ from RBCs is close to the residence time of the RBC in the coronary system. Sequential measurements of blood oxygen saturation (SO/sub 2/) are made when oxygenated blood is subjected to conditions similar to the myocardium. The natural logarithm of the relative value of the SO/sub 2/ at time t compared to the initial value of the SO/sub 2/ can be fitted to a straight line whose slope is proportional to the parameters of the RBC membrane, the sample size, the hematocrit and the diffusion parameters of the apparatus. This value is used to estimate the effect of cholesterol lowering treatments on O/sub 2/ release. This test will serve as a valuable adjunct to or replacement for stress tests in the evaluation of coronary artery disease, especially in patients whose physical condition make standard stress testing painful or risky.