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Objectives: The purpose of this study was to determine if combined intense lifestyle and pharmacologic lipid treatment reduce myocardial perfusion abnormalities and coronary events in comparison to usual-care cholesterol-lowering drugs and whether perfusion changes predict outcomes.Background: Lifestyle and lipid drugs separately benefit patients with coronary artery disease (CAD).Methods: A total of 409 patients with CAD, who underwent myocardial perfusion imaging by dipyridamole positron emission tomography at baseline and after 2.6 years, had quantitative size/severity of perfusion defects measured objectively by automated software with follow-up for five additional years for coronary artery bypass graft, percutaneous coronary intervention, myocardial infarction, or cardiac death. Patients were categorized blindly according to prospective, predefined criteria as "poor" treatment without diet or lipid drugs, or smoking; "moderate" treatment on American Heart Association diet and lipid-lowering drugs or on strict low-fat diet (<10% of calories) without lipid drugs; and "maximal" treatment with diet <10% of calories as fat, regular exercise, and lipid active drugs dosed to target goals of low-density lipoproteins <2.3 mmol/l (90 mg/dl), high-density lipoproteins >1.2 mmol/l (45 mg/dl), and triglycerides <1.1 mmol/l (100 mg/dl).Results: Over five years, coronary events occurred in 6.6%, 20.3%, and 30.6% of patients on maximal, moderate, and poor treatment, respectively (p = 0.001). Size/severity of perfusion abnormalities significantly decreased for patients receiving maximal treatment and increased for patients undergoing moderate and poor treatment (p = 0.003 and 0.0001, respectively). Combined intense lifestyle change plus lipid active drugs and severity/change of perfusion abnormalities independently predicted cardiac events.Conclusions: Intense lifestyle and pharmacologic lipid treatment reduce size/severity of myocardial perfusion abnormalities and cardiac events compared with usual-care cholesterol-lowering drugs. Perfusion changes parallel treatment intensity and predict outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization., Methods: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0., Results: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025)., Conclusions: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Data on impact of financial hardship on coronary artery disease (CAD) remain incomplete., Methods: Consecutive subjects referred for clinical rest/stress cardiac positron emission tomography (PET) were enrolled. Financial hardship is defined as patients' inability to pay for their out-of-pocket expense for cardiac PET. Abnormal cardiac PET is defined as at least moderate relative perfusion defects at stress involving > 10% of the left ventricle or global coronary flow reserve ≤ 2.0. Patients were followed for major adverse cardiovascular event (MACE) comprised of all-cause mortality, non-fatal myocardial infarction, and late coronary revascularization., Results: We analyzed a total of 4173 patients with mean age 65.6 ± 11.3 years, 72.2% men, and 93.6% reported as having medical insurance. Of these, 504 (12.1%) patients had financial hardship. On multivariable analysis, financial hardship associated with abnormal cardiac PET (odds ratio 1.377, p = 0.004) and MACE (hazard ratio 1.432, p = 0.010) and its association with MACE was mostly through direct effect with small proportion mediated by abnormal cardiac PET or known CAD., Conclusion: Among patients referred for cardiac rest/stress PET, financial hardship independently associates with myocardial perfusion abnormalities and MACE; however, its effect on MACE is largely not mediated by abnormal myocardial perfusion or known CAD suggesting distinct impact of financial hardship beyond traditional risk factors and CAD that deserves attention and intervention to effectively reduced adverse outcomes. Having medical insurance does not consistently protect from financial hardship and a more preventive-oriented restructuring may provide better outcomes at lower cost., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

For patients with a complete, chronic abducens nerve palsy and resulting abduction deficit, a transposition procedure is often the procedure of choice. One such transposition procedure involves transposing the superior rectus (SR) and inferior rectus (IR) laterally without disinserting or splitting either muscle. While effective, this procedure - like many transposition procedures - carries with it the risk of induced torsional or vertical misalignment. Here, we describe an adjustable variation of the above transposition procedure, one which potentially would allow for post-operative correction of induced vertical or torsional deviations.

Background: Subendocardial ischemia is commonly diagnosed but not quantified by imaging., Objectives: This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes., Methods: Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization., Results: Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ) >1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ >1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ >1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P < 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P < 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90)., Conclusions: Reduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization., Competing Interests: Funding Support and Author Disclosures Research supported by internal funds of the Weatherhead PET Center. Dr Gould has received internal funding from the Weatherhead PET Center and is the applicant for 510(k) U.S. Food and Drug Administration–cleared HeartSee K202679 PET software. Dr Johnson has received internal funding from Weatherhead PET Center for Preventing and Reversing Atherosclerosis and research support from St. Jude Medical (for CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology] trial; NCT02184117) and Volcano/Philips Corporation (for the DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses] trial; NCT02328820). To avoid any conflict of interest, Drs Gould, Nguyen, Johnson, and Kirkeeide waived their rights to the royalties that they were personally eligible to receive from sales of the intellectual property developed by them and licensed by the University of Texas Health Science Center (UTHealth) to third parties. UTHealth approved their request that all derived royalties be redirected to student scholarships or UTHealth’s Weatherhead PET Center research. UTHealth has a financial interest related to intellectual property via its affiliation with the UTHealth’s Weatherhead PET Imaging Center. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The literature reports no randomized trial in chronic coronary artery disease (CAD) of a comprehensive management strategy integrating intense lifestyle management, maximal medical treatment to specific goals and high precision quantitative cardiac positron emission tomography (PET) for identifying high mortality risk patients needing essential invasive procedures. We hypothesize that this comprehensive strategy achieves greater risk factor reduction, lower major adverse cardiovascular events and fewer invasive procedures than standard practice., Methods: The CENTURY Study (NCT00756379) is a randomized-controlled-trial study in patients with stable or at high risk for CAD. Patients are randomized to standard of care (Standard group) or intense comprehensive lifestyle-medical treatment to targets and PET guided interventions (Comprehensive group). Comprehensive Group patients are regularly consulted by the CENTURY team implementing diet/lifestyle/exercise program and medical treatment to target risk modification. Cardiac PET at baseline, 24-, and 60-months quantify the physiologic severity of CAD and guide interventions in the Comprehensive group while patients and referring physicians of the Standard group are blinded to PET results. The primary end-point is the CENTURY risk score reduction during 5 years follow-up. The secondary endpoint is a composite of death, non-fatal myocardial infarction, stroke, and coronary revascularization., Conclusions: The CENTURY Study is the first study in stable CAD to test the incremental benefit of a comprehensive strategy integrating intense lifestyle modification, medical treatment to specific goals, and high-precision quantitative myocardial perfusion imaging to guide revascularization. A total of 1028 patients have been randomized, and the 5 years follow-up will conclude in 2022., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose : To investigate the optimal time for Descemet membrane endothelial keratoplasty (DMEK) graft peeling, and to analyze the rolling properties of endothelial denuded grafts in a rabbit eye model. Materials and Methods : The vertical peeling force required to peel 1 mm wide Descemet membrane (DM) strips, was measured as the change in weight of the system during force application in a rabbit model. Twenty-one rabbit corneoscleral rims were stored in phosphate-buffered saline (PBS) at 4°C, and force analysis was performed at days 1, 5, or 21 after harvesting. After half of the strips of day 5 corneas were peeled and analyzed, the rims were moved to Optisol GS at 4°C, and the remaining strips were peeled off for force analysis at day 10. Separate DM grafts (n = 7) were analyzed by intraoperative optical coherence tomography (OCT) to determine the tissue rolling diameter before and after removal of endothelial cells by a swab. Unpaired t-test was used for statistical analysis. Results : There was a decrease in DM peeling force (p = .008) between days 1 and 5 (556.04 ± 111.76 and 324.30 ± 96.4 mg, respectively), and no difference between days 5 and 21 (p = .53). Peeling force for day 5 corneas placed in Optisol was higher at day 10 (324.30 ± 96.4 to 669.92 ± 166.24 mg, p = .005). The average rolling diameter of DM grafts was similar before and after the removal of endothelial cells (257.9 ± 131.1 and 249.8 ± 126.6 μm, respectively). Conclusions : DMEK Graft procurement could be potentially facilitated by lower DM-stromal adhesion strength at day five after obtaining corneoscleral rims, in a rabbit eye model. Time in the storage medium may influence adhesion strength. Endothelial cells do not appear to play a significant role in the rolling diameter of DM grafts.

Because randomized coronary revascularization trials in stable coronary artery disease (CAD) have shown no reduced myocardial infarction (MI) or mortality, the threshold of quantitative myocardial perfusion severity was analyzed for association with reduced death, MI, or stroke after revascularization within 90 d after PET. Methods: In a prospective long-term cohort of stable CAD, regional, artery-specific, quantitative myocardial perfusion by PET, coronary revascularization within 90 d after PET, and all-cause death, MI, and stroke (DMS) at 9-y follow-up (mean ± SD, 3.0 ± 2.3 y) were analyzed by multivariate Cox regression models and propensity analysis. Results: For 3,774 sequential rest-stress PET scans, regional, artery-specific, severely reduced coronary flow capacity (CFC) (coronary flow reserve ≤ 1.27 and stress perfusion ≤ 0.83 cc/min/g) associated with 60% increased hazard ratio for major adverse cardiovascular events and 30% increased hazard of DMS that was significantly reduced by 54% associated with revascularization within 90 d after PET ( P = 0.0369), compared with moderate or mild CFC, coronary flow reserve, other PET metrics or medical treatment alone. Depending on severity threshold for statistical certainty, up to 19% of this clinical cohort had CFC severity associated with reduced DMS after revascularization. Conclusion: CFC by PET provides objective, regional, artery-specific, size-severity physiologic quantification of CAD severity associated with high risk of DMS that is significantly reduced after revascularization within 90 d after PET, an association not seen for moderate to mild perfusion abnormalities or medical treatment alone., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Tufted capuchins (Cebus apella) were provided with a task that facilitated the use and modification of sticks as probing tools. It was found that subjects aged 10 years or older at initial task exposure were less likely to use tools than were younger subjects. Furthermore, juveniles whose mothers died before the subjects were aged 3 years were less likely to use tools than were juveniles whose mothers survived through this period. The ability to use tools was not related to subject sex or to access to the tool site or raw tool materials. Subjects modified tools both before and during their use, and the relative percentage of tools modified increased with subject age. Thus, it appears that capuchins most readily acquire tool use before the age of 10 years and that early disruption of the mother-infant relationship has deleterious effects on the emergence of instrumental behavior.

In 1987 and 1990 in Massachusetts, surveys were conducted to determine the size, pattern of distribution, and trends in the population of children assisted by medical technology. The authors obtained an unduplicated count of all Massachusetts children from 3 months to 18 years of age who used one or more of the following: tracheostomy, respirator, oxygen, suctioning, gastrostomy, jejunal or nasogastric feedings, ostomies, urethral catheterization, ureteral diversion, intravenous access, or dialysis. By comparing counts obtained from medical and educational sources, the authors were able to perform a capture-recapture analysis to estimate the overall number of children dependent upon these technologies. The number of children identified in our surveys increased from 1,085 in 1987 to 1,540 in 1990. However, the capture-recapture analysis yielded estimates of 2,147 plus or minus 230 for 1987 and 2,237 plus or minus 131 for 1990. This suggests that the population of children dependent upon medical technology was essentially stable during this period, and that the 42 percent increase in the number of children identified in our survey reflected improved sampling techniques. During the 3 years, shifts in the pattern of technology use were noted, however. Use of oxygen and gastrostomy increased, and urostomy use declined. A change in the age distribution of the children was also documented, with a shift in the preponderence of technology use from 12 to 24 months in 1987 to children in the first year of life in 1990. Using the 1990 estimate and the 1990 U.S. census figures, an overall prevalence estimate of 0.16 percent was calculated. Applying this to the U.S.child population yields an estimate of 101,800 children assisted by medical technology nationwide(assuming comparable technology use in other States). This information will facilitate policy analysis and program planning on regional and national levels for this medically complex group of children.

The increasing number of children assisted by medical technology in the U.S. has led to a need for systematic planning for the children's care in community settings such as schools. Project School Care in Massachusetts provides consultation to school systems as schools respond to the challenge of integrating children assisted by medical technology into educational settings. The model of practice described includes the step-wise planning process and the ensuing training, enrollment, and monitoring procedures. Implications are explored with particular emphasis on upgrading of skills at all medical and educational levels. More input from school health personnel in administrative decision-making around enrollment of children with special health care needs is recommended. For these children, a health care plan should be incorporated into their Individualized Education Plans and into their school records.

In April 1987, a census of children dependent on medical technology was carried out in Massachusetts to determine the one-month point prevalence. All medical and educational providers in the state who were likely to interact with such children were contacted and asked to complete a two-sided data form on youngsters (aged 3 months to 18 years) with tracheostomies, supplementary oxygen, respirators, suctioning, gastric feeding, central venous lines, ostomies, ureteral diversion, urethral catheterization and dialysis. Nearly 1250 children were found meeting these criteria. Capture-recapture analysis set the lower bound for technology dependence at 0.08% of the state's children. An analysis of the organ systems involved showed that 57% of the children had neurologic involvement--13% multisystem, 7% gastrointestinal-metabolic, 4% renal-genitourinary, and 3% musculoskeletal. Less than 1% of the children were reported as having immunologic or "other" disorders. Review of putative etiologies indicated that 45% of the children had congenital anomalies, 33% chronic medical diseases, 9% perinatal conditions, 7% hereditary-genetic disorders, 5% injuries, 2% infections, and 3% "other." The substantial prevalence of technology dependency among children creates challenges at the social, economic, and policy-making levels. It will be important to carry out systematic reporting and monitoring activities throughout time and across sites. This census is an example of one such statewide effort.

Potassium loss from damaged myocardial cells is linearly related to CPK enzyme loss reflecting extent of necrosis. The potassium analog, rubidium-82 (82Rb), is extracted after i.v. injection and retained in viable myocardium but is not trapped or washed out of necrotic regions. To compare myocardial cell metabolism with membrane dysfunction as indicators of necrosis/viability, 43 patients with evolving myocardial infarction and coronary arteriography had positron emission tomography using fluorodeoxyglucose (FDG) and the potassium analog 82Rb. Percent of heart showing FDG defects and 82Rb washout on sequential images indicating failure to retain the potassium analogue were visually assessed and quantified by automated software. Infarct size based on rubidium kinetics correlated closely with size and location on FDG images (visual r = 0.93, automated r = 0.82), suggesting that loss of cell membrane integrity for trapping the potassium analog 82Rb parallels loss of intracellular glucose metabolism, both comparable quantitative markers of myocardial necrosis/viability.

The Smart Chart has been an effective nutrition education tool with a wide variety of applications in establishing and achieving nutritional goals. It has been especially useful for the diabetic individual who is concerned about fats as well as sugars.

Experimental studies in animals have suggested that coronary flow reserve may be limited in patients with left ventricular hypertrophy (LVH). Accordingly, to noninvasively determine the effect of LVH on myocardial perfusion reserve, 25 patients, 9 with LVH and 16 controls, underwent positron imaging with rubidium-82 (82Rb) (30-55 mCi) or nitrogen-13 (13N) ammonia (12-19 mCi) at rest and following intravenous dipyridamole and handgrip stress. LVH was documented by echocardiographic and/or electrocardiographic measurements. LVH patients had either no chest pain (n = 8) and/or a normal coronary angiogram (n = 6). Nine simultaneous transaxial images were acquired, and the mean ratio of stress to rest activity (S:R), based on all regions for each heart, was calculated as an estimate of myocardial perfusion reserve. There were no regional differences in activity (i.e., perfusion defects) in any of the studies. S:R averaged 1.41 +/- 0.10 (s.d.) for controls and 1.06 +/- 0.09 for patients with LVH (p less than 0.0001). These data provide support for an abnormality in perfusion reserve in patients with LVH.

As a preliminary to a membrane oxygenator study, a study was made of clotting indices in dogs and their intercorrelation and relationship to human data. The most useful criterion for monitoring coagulation in experimental extracorporeal systems was sought. Linear regression and correlation analysis indicated that activated partial thromboplastin time (APTT) predicted whole blood clotting time with a correlation of 0.77 (p less than 0.01). Changes in the APTT with time after heparinization were similar to those previously reported in man, making the animal model an acceptable one for use in developing extracorporeal systems such as the membrane oxygenator. When blood activated recalcification time (BART), APTT, and whole blood clotting time (WBCT) assays were compared on the basis of applicability to studies of extracorporeal support, the APTT and the BART assays proved superior to the WBCT assay due to their reduced variability and increased speed of determination. The variability of the BART assay was the lowest, and its sensitivity was the same as the APTT assay. The principal drawback to the BART assay was not experienced in this study; that is, its dependence on adequate platelet levels which are unpredictable in extracorporeal systems.

The enhanced uptake and incorporation of 3H-glucosamine by guinea pig peritoneal exudate macrophages stimulated by macrophage-activating factor (MAF) were studied. MAF was produced by concanavalin A- (Con A) stimulated lymphocytes. Two systems were developed to assay this phenomenon, one using microtiter plates, the other using suspension cultures. Enhanced uptake of 3H-glucosamine by macrophages was found after 48-hr incubation in microtiter plates and after 24 hr in suspension cultures. Increased uptake of 14C-glucose and 3H-galactose was also observed under these conditions. The enhanced uptake of 3H-glucosamine was markedly reduced or abolished by the addition of glucose to the cell cultures or by replacement of the medium with fresh medium before pulsing with labeled sugar. These observations indicate that the mechanism of enhanced uptake reflects in part increased glucose utilization by the stimulated macrophages.