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Despite the increased availability of diagnostic tests for respiratory viruses, their clinical utility for children with community-acquired pneumonia (CAP) remains uncertain.To identify patterns of respiratory virus testing across children's hospitals prior to the COVID-19 pandemic and to determine whether hospital-level rates of viral testing were associated with clinical outcomes.Multicenter retrospective cohort study of children hospitalized for CAP at 19 children's hospitals in the United States from 2010-2019.Using a novel method to identify the performance of viral testing, we assessed time trends in the use of viral tests, both overall and stratified by testing method. Adjusted proportions of encounters with viral testing were compared across hospitals and were correlated with length of stay, antibiotic and oseltamivir use, and performance of ancillary laboratory testing.There were 46,038 hospitalizations for non-severe CAP among children without complex chronic conditions. The proportion with viral testing increased from 38.8% to 44.2% during the study period (p .001). Molecular testing increased (27.2% to 40.0%, p .001) and antigen testing decreased (33.2% to 7.8%, p .001). Hospital-specific adjusted proportions of testing ranged from 10.0% to 83.5% and were not associated with length of stay, antibiotic use, or antiviral use. Hospitals that performed more viral testing did not have lower rates of ancillary laboratory testing.Viral testing practices varied widely across children's hospitals and were not associated with clinically important process or outcome measures. Viral testing may not influence clinical management for many children hospitalized with CAP.

We describe ribavirin administration in hospitalized children over an 11-year period. Most patients were immunocompromised; there was variability in ribavirin use across hospitals. There was a clear shift toward the use of oral ribavirin despite a lack of evidence for its use.

To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019.The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment.We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 cases per 10 000 patient-days (95% CI, 4.03-5.93) in 2019 (P .001). C difficile-specific testing also decreased during the study period (P .001). Chronic gastrointestinal conditions (36%) and malignancy (32%) were the most common comorbidities in CDI encounters. Oral metronidazole use decreased during the study period (P .01) and oral vancomycin use increased (P .001).Our study demonstrates a decrease in CDI incidence in hospitalized pediatric patients, a notable change from prior studies, although this may have been influenced by altered testing patterns. We found a high incidence of CDI in patients with cancer and gastrointestinal conditions: groups that warrant targeted evaluation of CDI prevention and treatment.

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000 pd) varies widely among children’s hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (O:E) ratios were calculated by indirect standardization and compared with DOT/1000 pd. Outliers were defined by O:E z-scores. Antibacterial DOT/1000 pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552–679), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93–1.05). O:E ratios were moderately correlated with DOT/1000 pd (correlation estimate 0.44; 95% confidence interval, 0.19–0.64; P = .0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions.

Burn patients are at risk for bone disease due to aluminum (Al) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18-41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative Al only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age- and sex-matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age-matched volunteers at short-term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated Al in blood or urine; urine Al correlated inversely with serum osteocalcin. In 60% significant bone Al was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. Al loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors.

BMS-317180 (1) is a potent, orally active agonist of the human growth hormone secretagogue (GHS) receptor. This manuscript details the process research and development efforts that enabled the synthesis of the phosphate salt of 1 on a multi-kilogram scale. Key considerations in the development of this process focused on safe execution and the requirement for telescoped synthetic transformations (i.e., without isolation of intermediate products) to contend with a lack of suitably crystalline products.

Udgivelsesdato: 2008-Oct Energy loss is a well-established engineering concept that when applied to evaluating the performance of native heart valves and valvular prostheses has the potential for providing valuable information about the impact of valve function on myocardial performance. The concept has been understood for many years, but its routine application has been hindered not only by a lack of understanding of its meaning but also because of the lack of investigational tools to easily obtain the data necessary for its estimation. Today the gathering of that information is becoming easier, and thus the time has come to revisit the efficacy of energy loss for evaluating heart valve performance. This review defines what energy loss is, how it is measured, and how it might be applied to clinical situations of heart valve disease to better understand the impact of valvular disease on ventricular function.

uidelines for Reporting Mortality and Morbidity fter Cardiac Valve Interventions ary W. Akins, MD, D. Craig Miller, MD, Marko I. Turina, MD, icholas T. Kouchoukos, MD, Eugene H. Blackstone, MD, ary L. Grunkemeier, PhD, Johanna J. M. Takkenberg, MD, PhD, irone E. David, MD, Eric G. Butchart, MD, David H. Adams, MD, avid M. Shahian, MD, Siegfried Hagl, MD, John E. Mayer, MD, and ruce W. Lytle, MD The American Association for Thoracic Surgery, Beverly, Massachusetts; The Society of Thoracic Surgeons, Chicago, Illinois; and The European Association for Cardio-Thoracic Surgery, Windsor, Berks, United Kingdom

Previously, aortic valve stenosis (AS) etiology was usually congenital or due to rheumatic disease. However, the most frequent cause is now degenerative AS, which is often part of a continuum including increased rigidity of the aorta due to atherosclerosis and left ventricular dysfunction due to coronary artery disease. This article highlights newer approaches to quantify AS taking into account the inter-relation between the different components (valvular, vascular, and ventricular) affecting clinical outcome in these patients. Emphasis is given to a more comprehensive evaluation of AS severity going beyond classical measurements and including indices such as 1) the energy loss index to quantify the valvular obstruction net of pressure recovery; 2) systemic arterial compliance to quantify vascular load; and 3) valvular-arterial impedance to assess the global (valvular + vascular) increase in afterload. Routine use of these indices, easily measured by Doppler echocardiography, should improve clinical management of AS patients.

Background The need for bileaflet repair in bileaflet mitral valve prolapse (MVP) remains controversial. Will anterior leaflet prolapse resolve with posterior leaflet repair or should both leaflets be addressed? Single-leaflet MVP produces oppositely directed mitral regurgitant jets. Some patients show two crossed jets oppositely directed from the coaptation zone. We hypothesized that these indicate bileaflet lesions requiring complex repair. Methods Echocardiograms and surgical reports of 52 consecutive patients with MVP undergoing surgery were reviewed. Results First, all 14 patients with two oppositely directed jets had prolapse of more than one leaflet. Each jet was related to discrete leaflet distortions causing malcoaptation. Six underwent valve replacement. Seven had both leaflets repaired. One had posterior leaflet repair and annuloplasty, with persistent mitral regurgitation requiring valve replacement. Second, 36 of 38 patients with single jets had single-leaflet MVP. One underwent replacement; all others did well with single-leaflet repair. Two patients with bileaflet MVP but only one jet did well with single-leaflet repair or annuloplasty. Conclusion This crossed swords sign is an important clue to bileaflet mechanism of mitral regurgitation in MVP, associated with complex repair procedures. Thus, it provides a clue in the dilemma of bileaflet versus single-leaflet repair.

Background: Whether minimally diseased aortic valves should be replaced during other necessary cardiac operations remains controversial. Part of the decision-making process in that issue revolves around the risks of subsequent aortic valve replacement. This study evaluated the results of aortic valve replacement in patients following prior cardiac surgery. Methods: From February, 1984 through December, 2001 first-time aortic valve replacement was performed in 132 consecutive patients who had previous cardiac surgery utilizing cardiopulmonary bypass. Of those patients 89 (67%) had aortic valve replacement at a mean of 8.3 years after prior coronary artery bypass grafting, and 43 (33%) had aortic valve replacement at a mean of 13.0 years after previous procedures other than myocardial revascularization. Hospital records of all patients were retrospectively reviewed. Results: Early complications included operative mortality in six (6.7%) of the patients with prior coronary grafting and no mortality in the group with other prior operations. Patients having prior coronary grafting had more nonfatal complications than those with other previous procedures. Conclusions: Aortic valve replacement in patients following previous cardiac surgery can be accomplished with acceptable mortality and morbidity. Routine replacement of aortic valves that are minimally diseased during coronary artery bypass grafting may not be warranted.

Patients who survive out-of-hospital cardiac arrest are at high risk for recurrent arrest. Coronary artery bypass grafting (CABG) confers a survival advantage, but it is unclear whether antiarrhythmic drugs or an implanted defibrillator confer added benefit. This study was designed to determine predictors for further treatment, survival, and therapeutic internal cardiac defibrillator (ICD) discharge in this patient population.One hundred and eight patients undergoing CABG after out-of-hospital cardiac arrest were identified over a 12-year period. Case records were retrospectively reviewed. Follow-up was obtained and predictors of outcome events were analyzed.Fifty-four (50%) patients underwent CABG only. Fifty-four received additional treatment that included ICD placement in 23 (21%), antiarrhythmic medications in 19 (18%), or both in 12 (11%). Predictors of ICD placement included left ventricular ejection fraction (LVEF) less than 40% and perioperative intraaortic balloon counterpulsation. ICD or medical management increased survival in patients with LVEF40%. Predictors of increased mortality included age65 years, Cleveland Severity Score8, and female gender. Predictors of therapeutic ICD discharge included age65 years, reoperative CABG, LVEF40%, and positive postoperative electrophysiological (EP) study. No patient with a negative postoperative EP study received an ICD, and none suffered sudden cardiac death during follow-up.Patients with coronary artery disease anatomically suitable for CABG who survive an acute out-of-hospital cardiac arrest should undergo EP testing after CABG. Approximately half of these patients are adequately treated by CABG alone. The remainder may benefit from ICD placement or medical antiarrhythmic management.

Concomitant coronary artery disease with aortic valve disease is an established risk factor for diminished late survival. This study evaluated the results of bioprosthetic (BAVR) or mechanical aortic valve replacement (MAVR) performed with coronary artery bypass grafting (CABG).From January 1984 through July 1997, combined AVR + CABG was performed in 750 consecutive patients; 469 received BAVR and 281 received MAVR. BAVR recipients were significantly older (mean age, 75 vs 65 years), and had more nonelective operations, congestive heart failure, peripheral vascular disease, preoperative intraaortic balloons, lower cardiac indices, more severe aortic stenosis, less aortic regurgitation, and more extensive coronary artery disease.Early complications included operative mortality, 32 patients (4.3% total: 3.8% BAVR and 5.0% MAVR); perioperative infarction, 10 (1.3%); and perioperative stroke, 22 (2.9%). Significant multivariable predictors of early mortality were age, perioperative infarction or stroke, nonelective operation, operative year, ventricular hypertrophy, and need for intraaortic balloon. Ten-year actuarial survival was 41.7% for all patients. Predicted survival for age- and gender-matched cohorts from the general population versus observed survival were BAVR, 45% versus 36%; MAVR, 71% versus 48% (survival differences BAVR 9% vs MAVR 23%, p0.007). Significant multivariable predictors of late mortality included age, congestive failure, perioperative stroke, extent of coronary disease, peripheral vascular disease, and diabetes. Valve type was not significant. Ten-year actuarial freedom from valve-related complications were (BAVR vs MAVR) structural deterioration, 95% versus 100%, p = NS; thromboembolism, 86% versus 84%, p = NS; anticoagulant bleeding, 93% versus 88%, p0.005; reoperation, 98% versus 98%, p = NS.AVR + CABG has diminished late survival despite the type of prosthesis inserted. Although valve type did not predict late mortality, mechanical AVR was associated with worse survival compared with predicted and more valve-related complications due to anticoagulation requirements.

Background: Some patients with mitral stenosis (MS) have moderately reduced left ventricular (LV) ejection fraction (EF), due to either depressed myocardial contractility or alterations in loading conditions. The effect of moderately reduced LV EF on outcome after mitral valve replacement (MVR) is not known. Methods: We studied 16 consecutive patients with LV EF ≤0.50 and MS without significant mitral regurgitation or other valvular or coronary artery disease (Group I). We selected four controls with LV EF >0.50 for each patient, matched for time of surgery (Group II, n = 64). Mean EF in Groups I and II was 0.45 and 0.66, respectively. We compared short- and long-term outcome between the two groups. Results: There were no perioperative deaths. Group I patients had a higher incidence of in-hospital postoperative heart failure (25% vs. 6%, P = 0.02). Mean follow-up was 9 years in both groups. Mean New York Heart Association class improved from 2.4 to 1.7 in both groups. Group I patients had a higher incidence of heart failure deaths (13% vs. 2%, P = 0.03) and admissions (40% vs. 13%, P = 0.01). There were, however, no differences between Groups I and II in overall mortality (27% vs. 21%), rate of cardiac admissions (69% vs. 53%), or mean Specific Activity Scale Score (2.5 vs. 2.5). Conclusions: Although patients with MS and moderately reduced LV EF are at higher risk for heart failure after MVR, overall mortality is not different from that of patients with normal EF. Moderate depression of LV EF should not be a contraindication to MVR for MS.

To determine the rate of return visits to pediatric emergency departments (EDs) and identify patient- and visit-level factors associated with return visits and hospitalization upon return.Retrospective cohort study of visits to 23 pediatric EDs in 2012 using data from the Pediatric Health Information System.Patients18 years old discharged following an ED visit.The primary outcomes were the rate of return visits within 72 hours of discharge from the ED and of return visits within 72 hours resulting in hospitalization.1,415,721 of the 1,610,201 ED visits to study hospitals resulted in discharge. Of the discharges, 47,294 patients (3.3%) had a return visit. Of these revisits, 9295 (19.7%) resulted in hospitalization. In multivariate analyses, the odds of having a revisit were higher for patients with a chronic condition (odds ratio [OR]: 1.91, 95% confidence interval [CI]: 1.86-1.96), higher severity scores (OR: 1.42, 95% CI: 1.40-1.45), and age1 year (OR: 1.32, 95% CI: 1.22-1.42). The odds of hospitalization on return were higher for patients with higher severity (OR: 3.42, 95% CI: 3.23-3.62), chronic conditions (OR: 2.92, 95% CI: 2.75-3.10), age1 year (1.7-2.5 times the odds of other age groups), overnight arrival (OR: 1.84, 95% CI: 1.71-1.97), and private insurance (OR: 1.47, 95% CI: 1.39-1.56). Sickle cell disease and cancer patients had the highest rates of return at 10.7% and 7.3%, respectively.Multiple patient- and visit-level factors are associated with revisits. These factors may provide insight in how to optimize care and decrease avoidable ED utilization.

We have utilized clonal lines of the rat osteoblastic cell line ROS 17/2.8 stably transfected with full-length parathyroid hormone-related protein (PTHrP) cDNA in a sense or an antisense orientation to examine the effects of alteration in the production of endogenous PTHrP on expression of the PTH/PTHrP receptor. In the stably transfected clonal cell lines, changes in PTH/PTHrP receptor expression were evaluated by Northern blot analysis, whole-cell ligand binding of 125I-[Tyr36] PTHrP (1-36), and exogenous PTHrP (1-34)-stimulated cyclic adenosine monophosphate (cAMP) accumulation. Compared to control (vector-transfected) cells, PTHP-overproducing (sense-transfected) cells exhibited a marked decrease in the expression of PTH/PTHrP receptor mRNA and PTHrP ligand binding, as well as a corresponding decrease in the PTHrP (1-34)-stimulated cAMP response. By contrast, the antisense-transfected cells showed a marked increase in expression of PTH/PTHrP receptor mRNA and PTHrP (1-34) ligand binding, but a significant increase in the PTHrP (1-34)-stimulated cAMP response was not detected. Using antisense-transfected ROS cells, PTH/PTHrP receptor mRNA expression and 125I-[Tyr36] PTHrP (1-36) binding were downregulated by treatment for 24 h with exogenous PTHrP (1-36), forskolin, or dibutyryl cAMP. The findings extend those of earlier studies showing receptor downregulation by exogenous PTH by indicating that endogenous PTHrP, as well as circulating PTH, may help regulate receptor production; and suggesting that even very low concentrations of the peptide may influence receptor production.

The more extensive conflict of interest information will permit reviewers and editors to ensure the accuracy, balance,and lack of bias of papers accepted for publication.Therefore, a brief conflict statement will be published on the cover page and a more extensive description will be published at the end of the paper to allow concerned readers to make their own judgments about the quality of the information reported.

Because the elderly are increasingly referred for operation, we reviewed results with cardiac surgical patients 80 years old or older.Records of 600 consecutive patients 80 years old or older having cardiac operations between 1985 and 1995 were reviewed. Follow-up was 99% complete.Two hundred ninety-two patients had coronary grafting (CABG), 105 aortic valve replacement (AVR), 111 AVR + CABG, 42 mitral valve repair/ replacement (MVR) +/- CABG, and 50 other operations. Rates of hospital death, stroke, and prolonged stay (14 days) were as follows: CABG: 17 (5.8%), 23 (7.9%) and 91 (31.2%); AVR: 8 (7.6%), 1 (1.0%), and 31 (29.5%); AVR + CABG: 7 (6.3%), 12 (10.8%), and 57 (51.4%); MVR +/- CABG: 4 (9.5%), 3 (7.1%), and 16 (38.1%); other: 9 (18.0%), 3 (6.0%), and 23 (46.0%). Multivariate predictors (p0.05) of hospital death were chronic lung disease, postoperative stroke, preoperative intraaortic balloon, and congestive heart failure; predictors of stroke were CABG and carotid disease; and predictors of prolonged stay were postoperative stroke and New York Heart Association class. Actuarial 5-year survival was as follows: CABG, 66%; AVR, 67%; AVR + CABG, 59%; MVR +/- CABG, 57%; other, 48%; and total, 63%. Multivariate predictors of late death were renal insufficiency, postoperative stroke, chronic lung disease, and congestive heart failure. Eighty-seven percent of patients believed having a heart operation after age 80 years was a good choice.Cardiac operations are successful in most octogenarians with increased hospital mortality, postoperative stroke, and longer hospital stay. Long-term survival is largely determined by concurrent medical diseases.

Objectives: A total of 4756 cases of intraaortic balloon pump support have been recorded at the Massachusetts General Hospital since the first clinical insertion for cardiogenic shock in 1968. This report describes the patterns of intraaortic balloon use and associated outcomes over this time period. Methods: A retrospective record review was conducted. Results: Balloon use has increased to more than 300 cases a year at present. The practice of balloon placement for control of ischemia (2453 cases, 11.9% mortality) has become more frequent, whereas support for hemodynamic decompensation (congestive heart failure, hypotension, cardiogenic shock) has been relatively constant (1760 cases, 38.2% mortality). Mean patient age has increased from 54 to 66 years, and mortality has fallen from 41% to 20%. Sixty-five percent (3097/4756) of the total patient population receiving balloon support underwent cardiac surgery. Placement before the operation (2038 patients) was associated with a lower mortality (13.6%) than intraoperative (771 patients, 35.7% mortality) or postoperative use (276 patients, 35.9% mortality). Independent predictors of death with balloon pump support were insertion in the operating room or intensive care unit, transthoracic insertion, age, procedure other than angioplasty or coronary artery bypass, and insertion for cardiogenic shock. Independent predictors of death with intraoperative balloon insertion were age, mitral valve replacement, prolonged cardiopulmonary bypass, urgent or emergency operation, preoperative renal dysfunction, complex ventricular ectopy, right ventricular failure, and emergency reinstitution of cardiopulmonary bypass. Conclusions: Balloons are being used more frequently for control of ischemia in more patients who are elderly with lower mortality. An institutional bias toward preoperative use of the balloon pump appears to be associated with improved outcomes. (J Thorac Cardiovasc Surg 1997;113:758-69)

A well differentiated human hepatoma cell line (Hep G2) was used to explore potential roles for PTH-related peptide (PTHrP) as an autocrine/paracrine growth factor. Using Northern analysis or reverse transcription-PCR, Hep G2 cells were found to express messenger RNAs for both PTHrP and the cloned PTH/PTHrP receptor, and the cells exhibited specific binding for [125I]PTHrP(1-36). Hep G2 growth medium was found to contain relatively large amounts of immunoreactive PTHrP (30 vs. 1-2 pM in medium not exposed to cells), and the PTHrP in growth medium (conditioned medium) was shown to contain N-terminal PTHrP biological activity, as assessed by the ability of the medium to stimulate cAMP production in rat osteosarcoma cells (ROS 17/2.8). Conditioned medium produced a dose-dependent severalfold increase in ROS cell cAMP that could be blocked by the PTHrP receptor antagonist [Asn10,Leu11,DTrp12]PTHrP-(7-34). PTHrP in Hep G2 cells also was detected by immunocytochemistry using antiserum to either synthetic PTHrP-(1-34) or recombinant PTHrP-(-5 to 139). Furthermore, these antisera were found to inhibit the ability of PTHrP-(1-34) to stimulate ROS cell cAMP production. When either antiserum (1:800-1:100 dilution) was added to subconfluent Hep G2 cells in medium containing 5% FBS for 3 days, a dose-related 40-50% increase in cell number occurred that could be inhibited by concurrent addition of 10 microM synthetic PTHrP-(1-36). The results show that Hep G2 cells synthesize and secrete both immunoreactive and biologically active PTHrP. As neutralization of PTHrP secreted by these cells by the addition of antiserum to PTHrP resulted in increased cell growth, the findings suggest that PTHrP can function as an autocrine or paracrine growth factor to suppress the growth of these human hepatoma cells.

The Society of Thoracic Surgeons Clinical Practice Guidelines are intended to assist physicians and other health care providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. These guidelines should not be considered inclusive of all proper methods of care or exclusive of other methods of care reasonably directed at obtaining the same results. Moreover, these guidelines are subject to change over time, without notice. The ultimate judgment regarding the care of a particular patient must be made by the physician in light of the individual circumstances presented by the patient.

Mechanical cardiac valvular prostheses continue to be more popular than bioprostheses for heart valve replacement operations. Five different brands of mechanical heart valves are now approved for implantation in the United States: Starr-Edwards models 1260 and 6120, Medtronic-Hall, St. Jude Medical, Omniscience, and CarboMedics. Each model of mechanical valve has certain positive and negative attributes, but none is functionally mechanically perfect. A review of the published long term results with these valves favors the Medtronic-Hall and St. Jude Medical valves. A new method of assessing the thrombogenic potential and requirement for anticoagulation of the different mechanical valves, namely the composite thromboembolism and bleeding index, is proposed. Evaluation of the new index demonstrates a modest advantage for the Medtronic-Hall valve, particularly in the aortic position.

subspecialty practice more important. Clearly, both approaches are considered valid by other Boards and by the ABMS. The current ABTS approach of a comprehensive exam derived from SESATS has been associated with a high pass rate and general approval from diplomates. The ABTS will continue to consider the validity of the two approaches but has also been advised by our psychometrician to gain further experience with the comprehensive exam before considering any change. If undertaken, transition to a modular exam would require a much larger pool of exam questions with subspecialty-focused questions of far greater difficulty than used currently.

Between January 1985 and June 1992, 263 consecutive patients had mitral valve reconstruction (133 patients) or replacement (130 patients) for degenerative or ischemic mitral regurgitation. The two groups were similar in sex, age, prior infarctions or cardiac operations, hypertension, angina, and functional class. Both groups were similar in mean ejection fraction, pulmonary artery pressure, cardiac index, and incidence of coronary artery disease. More reconstruction than replacement patients had ischemic etiology (22 [16%] versus 12 [9%]; p = not significant), and fewer reconstruction patients had ruptured anterior leaflet chordae (9 [7%] versus 39 [30%]; p0.01). More reconstruction than replacement patients had concomitant cardiac procedures (67 [50%] versus 59 [45%]; p = not significant). Hospital death occurred in 4 reconstruction patients (3%) and 15 (12%) replacement patients (p0.01). Median postoperative stay was shorter in reconstruction patients (10 versus 12 days; p = 0.02). Late valve-related death occurred in 3 reconstruction patients (2%) and 8 (6%) replacement patients (p = 0.08). Six-year actuarial freedom from thromboembolism was 92% for the reconstruction group and 85% for the replacement group (p = 0.12). Freedom from all valve-related morbidity and mortality was 85% for the reconstruction patients and 73% for the replacement patients (p = 0.03). Significant multivariate predictors of hospital death were age, mitral valve replacement, functional class, congestive heart failure, no posterior chordal rupture, and nonelective operation. Mitral valve reconstruction, when technically feasible, is the procedure of choice for degenerative or ischemic mitral regurgitation because of significantly lower hospital mortality and late valve-related events.

To assess the changing trends in patient profiles, operative indications and techniques, and their impact on the results of reoperative myocardial revascularization, we reviewed the records of 750 consecutive patients who had an isolated first reoperation for coronary artery disease at the Massachusetts General Hospital from 1977 to 1992. The patients were chronologically grouped into three equal cohorts of 250 patients. Our assessment over time revealed a significantly (p0.03) increased incidence of the following: older age, peripheral vascular disease, grafts at the first revascularization, longer operative interval, interval infarctions and angioplasties, and congestive heart failure and unstable angina requiring greater use of preoperative intraaortic balloon pumping. At catheterization significantly more left main coronary disease, lower ejection fractions, and more patent but diseased grafts were found. The reoperations were significantly done more urgently, with more grafts placed and a greater use of mammary artery grafting. Despite these increased risks over time, median postoperative hospital stay was significantly shortened (p0.001), though hospital mortality (5.3%) and perioperative myocardial infarction (6.3%) did not change significantly. Significant multivariate predictors of hospital death were nonelective operation, perioperative myocardial infarction, prior myocardial infarction, and mammary artery grafting at the initial operation.

Physiological roles for PTH-related peptide (PTHrP) appear varied, but remain to be clarified. The peptide is present in large amounts in milk, and PTHrP mRNA has been shown to be present in high amounts in lactating mammary gland. Because PTHrP can cause smooth muscle relaxation, we hypothesized that the peptide might affect the contractility of the breast myoepithelial cell and thereby affect milk ejection. To test this idea, we asked whether PTHrP might affect second messenger responses in a human mammary gland myoepithelial-cell line (Hs578Bst) derived originally from normal breast tissue. To verify the presumed origin of these cells, we also examined the effects of oxytocin. Cells were grown in culture in multiwell plates and exposed to test peptides for 15 min in buffer containing 1 mM isobutylmethylxanthine, and intracellular cAMP was measured by RIA. Both PTHrP-(1-34) and PTH-(1-34) increased cAMP in a dose-related fashion (ED50, 5 nM), with a maximal effect (3-fold) occurring at 100 nM. The ability of PTHrP to stimulate cAMP was inhibited by a 10- to 100-fold molar excess of the specific inhibitors, PTH-(3-34) or PTHrP-(7-34). Inhibitors alone did not alter cAMP. Oxytocin also produced an increase in cAMP, but the effect was inconsistent and occurred only with high doses (0.1-1 microM). Using cells grown on coverslips and loaded with fura-2AM, intracellular Ca2+ was monitored in cells exposed to test peptides. Oxytocin (0.2-20 nM) produced rapid dose-related increases in intracellular Ca2+, with a peak and plateau characteristic of initial mobilization of intracellular Ca2+, followed by entry of extracellular Ca. The plateau was eliminated by the Ca channel antagonist La3+ or by perfusion of cells with Ca-free medium. PTHrP (10-100 nM) altered the intracellular Ca2+ response to oxytocin in 66% of 39 preparations tested. PTHrP inhibited the Ca2+ response when given before oxytocin or transiently decreased the plateau phase of the Ca2+ response when given after oxytocin. Analysis of cellular mRNA using reverse transcription polymerase chain reaction indicated that these cells express the gene for PTHrP, and immunohistochemistry using antiserum to PTHrP revealed positive staining of cells. Measurement of immunoreactive PTHrP in conditioned medium confirmed that these cells can synthesize and secrete the peptide. The finding of a response of this cell line to oxytocin provides functional evidence of their myoepithelial derivation.(ABSTRACT TRUNCATED AT 400 WORDS)

Vasoactive intestinal peptide (VIP) is a widely distributed neuropeptide that has been considered a potential regulator of cell growth and differentiation in various tissues, including the gut. To examine this idea, we used a human colon carcinoma cell line (LoVo) as a model system and measured ornithine decarboxylase (ODC), because this is the rate-limiting enzyme for the formation of polyamines, which are thought to be key factors in regulating cell growth. LoVo cells, grown to about 80% confluence in F-12 medium containing 10% fetal bovine serum, were preincubated for 5 h in low serum medium (1% fetal bovine serum in F-12), and ODC activity was determined by measuring 14CO2 liberated from 14C-labeled ornithine. VIP caused a dose-related biphasic change in ODC, with activity increased at 10 pM, maximal (5-fold increase) at 10 nM, and decreased toward basal at 100 nM to 1 microM. Incubation of cells for 6 days with VIP in low serum medium showed similar changes in cell numbers, with growth being increased by doses in the 1 pM to 100 nM range and decreased at higher doses (greater than or equal to 100 nM). Exposure of cells to 5 mM alpha-difluoromethylornithine blocked both the VIP-induced increase in cell number and the VIP-induced increase in ODC activity. Increased ODC mRNA was detected after 2 h of exposure to VIP, a time at which ODC activity peaked after treatment, and the increase in ODC mRNA caused by VIP was dose-dependent. In related experiments LoVo cells were found to have high affinity VIP receptors (Kd = 0.4 nM), as assessed by examination of [125I]VIP binding in the presence of varying concentrations of unlabeled VIP. Studies of intracellular cAMP revealed a dose-related increase in cAMP in response to VIP (ED50 = 11 pM), and the adenylate cyclase activator forskolin increased both ODC activity and ODC mRNA. The findings support the idea that LoVo cells have VIP receptors linked to cAMP which can stimulate cell growth at least in part by increasing ODC synthesis and activity, thereby altering the production of polyamines. The decreased growth and ODC activity observed with high doses of VIP may involve a second messenger other than cAMP.

Study objective: To evaluate the safety and effectiveness of temporary IV antihypertensive therapy in patients with acute traumatic thoracic aortic disruption. Design: Retrospective chart review of all patients treated for proven traumatic aortic disruption during the ten-year period of 1980 through 1989. Setting: Emergency department of a large, urban, Level I trauma center. Interventions: Preoperative IV β-blockade and nitroprusside after initial resuscitation in hemodynamically stable patients. Results: Thirty-seven patients with angiographically proven aortic disruption were separated retrospectively into one of three groups. Group 1 (15 patients without preoperative antihypertensive therapy) had two deaths. Group 2 (15 patients treated for two to seven hours [mean, 3.8 hours] before surgery with antihypertensives) had one death. Group 3 (seven patients treated with antihypertensives for 24 hours to four months before surgery to allow recovery from associated severe injuries) had one death. There were no complications resulting from antihypertensive therapy. Conclusion: Temporary antihypertensive therapy appears to be safe and effective in patients with aortic disruption.

We managed 51 patients with thoracic aortic injuries caused by blunt trauma between 1977 and 1990. Fortynine injuries were located in the upper descending aorta and one each in the ascending aorta and anatic arch. Three patients arrived moribund and underwent thoracotomy for resuscitation, and all died. The diagnosis was confirmed by aortography in 48. One patient died of aortic rupture, 1 died of hypoxemia, and 1 refused operation and died. Forty-four patients had aortic repair, 42 with graft insertion. Gott shunts were placed in 23 with 3 cases of paraplegia (13%). Simple cross-clamping was used in 19 with 1 case of paraplegia (5.2%). We found statistically significant differences between the cross-clamp times of patients without paraplegia compared with those in whom paraplegia developed in both the shunt and no-shunt groups. Logistic regression analysis showed that the only factor significantly associated with paraplegia was cross-clamp time. There were two postoperative deaths (4.4%). Seven patients had medical therapy initially and aortic repair was delayed to allow other injuries to stabilize. Before aortic repair, 18 patients had intraarterial pressure monitoring and 34 received β-blockers or antihypertensive drugs. We conclude that aortic repair with graft insertion is usually successful in nonmoribund patients, simple crossclamping is associated with a relatively low risk of paraplegia, the incidence of paraplegia is directly associated with the duration of cross-clamp time, and selected patients can be managed medically while awaiting aortic repair.

Mitral regurgitation affects more than 2 million people in the USA. The main causes are classified as degenerative (with valve prolapse) and ischaemic (ie, due to consequences of coronary disease) in developed countries, or rheumatic (in developing countries). This disorder generally progresses insidiously, because the heart compensates for increasing regurgitant volume by left-atrial enlargement, causes left-ventricular overload and dysfunction, and yields poor outcome when it becomes severe. Doppler-echocardiographic methods can be used to quantify the severity of mitral regurgitation. Yearly mortality rates with medical treatment in patients aged 50 years or older are about 3% for moderate organic regurgitation and about 6% for severe organic regurgitation. Surgery is the only treatment proven to improve symptoms and prevent heart failure. Valve repair improves outcome compared with valve replacement and reduces mortality of patient with severe organic mitral regurgitation by about 70%. The best short-term and long-term results are obtained in asymptomatic patients operated on in advanced repair centres with low operative mortality (1%) and high repair rates (/=80-90%). These results emphasise the importance of early detection and assessment of mitral regurgitation.

Mechanical cardiac valvular prostheses currently enjoy a 60% to 40% market-share advantage over tissue prostheses in the United States and worldwide. Only the Starr-Edwards caged Silastic (Dow Corning) ball, Medtronic-Hall, St. Jude Medical, and Omniscience valves remain available in the United States. Although each valve has certain advantages and disadvantages, no design has achieved functional mechanical perfection. Late follow-up of valve-related complications from the literature favors the St. Jude Medical and Medtronic-Hall valves.

To determine the safety of intraaortic balloon pump catheter insertion for critical coronary ischemia through suprainguinal prosthetic bypass grafts, we examined our experience of 19 intraaortic balloon pumps placed through grafts in 17 patients by means of surgical exposure (8) or the percutaneous (11) approach. Fourteen intraaortic balloon pumps were placed through matured grafts at a time remote (2 to 13 years; mean, 7 years) from their vascular bypass surgery. Five were inserted through nonmatured grafts during the same hospitalization as their vascular reconstructive surgery (1 to 12 days; mean, 4 days). One patient, a day after an aortoiliac bypass, died during an urgent, surgical intraaortic balloon pump insertion for cardiogenic shock. All other patients had prompt reversal of their cardiac ischemia. Decreased limb perfusion developed during use of the intraaortic balloon pump in three patients, all of whom had their intraaortic balloon pump placed percutaneously through mature grafts. Two of these required surgical thrombectomy. Ten intraaortic balloon pump insertions in eight patients survived the hospitalization and were followed for a mean of 24 months (range, 2 weeks to 64 months). No localized groin or graft infections were identified. No bleeding complications or pseudoaneurysms occurred. Thus in patients with unstable, severe, cardiac disease, intraaortic balloon pumps can be safely placed through indwelling suprainguinal bypass grafts. (J VASC SURG 1991;13:830-7.)

Whole blood (WB) ex vivo stimulation assays are useful for measuring cytokine responses due to the easy access of samples from healthy donors and patients and the minimal processing of the sample required. Because the assay mimics the natural environment, WB culture may be the best milieu in which to study cell activation and cytokine production in vitro. Whole blood stimulation has been used to investigate the cellular responsiveness to a variety of stimuli, including bacterial endotoxin (LPS), antigens, allergens, and antibiotics. Various clinical uses of whole blood stimulation assays have been suggested, including the assessment of autoimmune diseases, the monitoring of drug and vaccine efficacy, and immunotoxicity. Thus, whole blood cell culture may be useful in studying the biological effects of potential allergenic and/or antigenic substances or drugs on immune cell activation and cytokine secretion.

Although the incidence of paravalular leaks, the most common cause of non-structural dysfunction after valve replacement, is well defined, the results of their surgical correction are not. Given the growing enthusiasm for interventional catheter-based correction of paravalvular leaks, a current surgical baseline against which to compare these results is important.All patients who had surgical correction of an aortic or mitral paravalvular leak unrelated to acute bacterial endocarditis between 1986 and 2001 were identified from a computerized registry. Hospital records were reviewed, and follow up data obtained.A total of 136 consecutive patients (73 males, 63 females; mean age 64 years) underwent surgical correction of a paravalvular leak. Of the valves, 44 (32%) were aortic and 92 (68%) mitral. More than one previous cardiac operation had been performed in 68 patients (50%). In 107 patients (79%; 32 aortic (73%), 75 mitral (82%)), the leak was the primary indication for reoperation, while for 29 patients (21%; 12 aortic (27%), 17 mitral (18%)) the correction was secondary to another cardiac procedure. In 65 patients (48%; 12 aortic (27%), 53 (58%) mitral)) the leak was repaired primarily, while in 71 patients (52%; 32 aortic (73%), 39 (42%) mitral)) the prosthesis was replaced. Operative mortality was 6.6% (n = 9). There were no significant multivariable predictors of hospital death. Perioperative stroke occurred in seven cases (5.1%), and hospital stay was14 days in 40 patients (29%). The 10-year Kaplan-Meier survival was 30 (CI 20-39)%. Ten-year actual versus actuarial freedom from repeat paravalvular leak was 84 (CI 68-92)% versus 63 (CI 49-76)%.Surgical correction of cardiac paravalvular leaks can be performed with acceptable mortality and morbidity. Patients with surgically corrected paravalvular leaks have a limited life expectancy, but reasonable freedom from recurrent paravalvular leak.

Background We sought to characterize patient survival and degree of late mitral regurgitation (MR) in patients undergoing surgical revascularization with moderate ischemic MR. Methods We retrospectively reviewed 251 patients undergoing coronary artery bypass graft (CABG) surgery between 1991 and 2001 with 3+ ischemic MR, including 31 patients who had concomitant mitral annuloplasty. Univariate and multivariable testing was employed. Results Actuarial 1-, 5-, and 10-year survival was 84.0%, 67.5%, and 37.1% in the overall group of 251 patients. Independent predictors of long-term mortality were age 70 years or more (hazard ratio 2.50 [95% confidence interval 1.82 to 3.44]), prior myocardial infarction (3.99 [2.15 to 7.39]), unstable angina (2.27 [1.69 to 3.04]), chronic renal failure (4.87 [3.13 to 7.58]), atrial fibrillation (2.21 [1.65 to 2.96]), left internal mammary artery to left anterior descending artery graft (0.28 [0.18 to 0.43]), preoperative β-blocker (0.43 [0.28 to 0.67]), ejection fraction (0.71/10% [0.64 to 0.80]), left atrium size (0.88/mm [0.84 to 0.92]), diffuse wall motion abnormalities (2.83 [1.77 to 4.55]), and mitral leaflet restriction (3.85 [2.46 to 5.99]). The model controlled for the performance of annuloplasty, which did not emerge as an independent predictor. Patients undergoing annuloplasty did have less mean late MR than those having CABG alone ( p = 0.005). Overall, 57.8% of patients (63 of 109) with follow-up echocardiograms had improvement in grade of MR compared with baseline. In 54 of 95 patients (56.8%), intraoperative transesophageal echocardiography downgraded the degree of MR compared with the preoperative study. Conclusions Patients with moderate ischemic MR undergoing CABG had relatively poor long-term survival, with significant differences when stratified according to preoperative characteristics. Performance of mitral annuloplasty reduced the degree of regurgitation but was not a predictor of long-term survival. Intraoperative transesophageal echocardiography frequently downgraded the degree of MR.

Background . Wound complications associated with long incisions used to harvest the greater saphenous vein are well documented. Recent reports suggest that techniques of endoscopic vein harvest may result in decreased wound complications. A prospective, nonrandomized study was developed to compare outcomes of open versus endoscopic vein harvest procedures. Methods . There were 106 patients in the open vein harvest group, and 154 patients in the endoscopic vein harvest group. Patient characteristics and demographics were similar in both groups. Wound complications identified were dehiscence, drainage for greater than 2 weeks postoperatively, cellulitis, hematoma, and seroma/lymphocele. Results . Wound complications were significantly less in the endoscopic vein harvest group (9 of 133, 6.8%) versus the open vein harvest group (26 of 92, 28.3%), p less than 0.001. By multivariable analysis with logistic regression, the open vein harvest technique was the only risk factor for postoperative leg wound complication (relative risk 4.0). Conclusions . Endoscopic vein harvest offered improved patient outcomes in terms of wound healing compared with the open vein harvest technique.

The present experiments examined the potential ability of parathyroid hormone-related protein (PTHrP) to influence growth of the human colon cancer cell HT-29 and the ability of the cell to adhere to several extracellular matrix (ECM) proteins found in normal tissues. Addition of PTHrP analogs, PTHrP (1-34), PTHrP (67-86), or PTHrP (107-139), to HT-29 cells in culture did not influence cell growth or the adhesion of the cells to wells coated with fibronectin, laminin, or collagen type I. Likewise, in HT-29 cells induced to overexpress PTHrP by stable transfection with PTHrP cDNA, compared to vector-transfected control HT-29 cells, no effect on cell growth occurred. However, in the transfected cells, the increased production of PTHrP significantly enhanced cell adhesion to type I collagen but not to fibronectin or laminin. The results raise the possibility that PTHrP might play a role in colon tumor invasion and metastasis by influencing cell adhesion to specific extracellular matrix proteins.

The rat intestinal cell line, IEC-6, was used as a model to study effects of parathyroid hormone-related protein (PTHrP) on crypt cell growth. Studies showed that addition of PTHrP analogs (1-34), (67-86), or (107-139) to growth medium did not affect proliferation of cells grown in either high (10% Nu-Serum) or low serum (1% Nu-Serum). However, studies on clonal lines of IEC-6 cells stably transfected with PTHrP cDNA and overexpressing PTHrP showed that increased PTHrP production enhanced cell growth and 3H-thymidine incorporation in high, but not low, serum. Additional studies examined the role of the nuclear localization sequence (NLS) of PTHrP in mediating the growth effect. In three clonal IEC-6 lines transfected with PTHrP cDNA bearing a mutated NLS, the ability of PTHrP to stimulate 3H-thymidine incorporation and cell growth was lost. The results suggest that endogenously produced PTHrP can promote proliferation of IEC-6 cells and that the integrity of the NLS of PTHrP is required for its growth effects.

The increasing risk of perioperative stroke after coronary artery bypass grafting can in part be attributed to the increased incidence of carotid stenosis with increasing patient age. The efficacy of carotid endarterectomy has been demonstrated for both symptomatic and asymptomatic patients. Combined operations yield acceptable mortality and stroke risks, provide good freedom from late events, and cost less than staged operations.

Background. Aortic root replacement in patients who have undergone previous aortic root replacement presents a formidable technical challenge, which may lead to increased surgical mortality. Methods. We reviewed our experience from January 1989 through November 1995. Seven consecutive patients (6 men and 1 woman) underwent eight repeat aortic root replacements. Mean follow-up was 19 months. Previous root replacement had been performed with homograft in 1 patient, with a bioprosthetic valve composite graft in 1 patient, and with a mechanical valve composite graft in 6 patients. The techniques used at the previous procedures were the Cabrol technique (2 patients), Bentall technique (3 patients), and the coronary button technique (3 patients). Reoperation was indicated for pseudoaneurysm formation in 4 patients and for endocarditis in the others. Results. Aortic homografts were implanted in all patients with endocarditis and mechanical valve composite grafts were used in the others. In all reoperations, the coronary button technique was used. No procedures were done emergently. Concomitant procedures were performed in 2 patients, including mitral valve replacement and aortic arch aneurysm repair. One patient had recurrence of his endocarditis 36 months after operation because of continued intravenous drug use requiring a second successful homograft root replacement. There were no early deaths and one late death at 16 months after operation. Conclusions. Repeat aortic root replacement, even in the setting of endocarditis, can be done with low mortality.

One factor influencing the choice of mechanical versus bioprosthetic valves is reoperation for bioprosthetic valve failure. To define its operative risk, we reviewed our results with valve reoperation for bioprosthetic valve failure.Records of 400 consecutive patients having reoperative mitral, aortic, or mitral and aortic bioprosthetic valve replacement from January 1985 to March 1997 were reviewed.Reoperations were for failed bioprosthetic mitral valves in 219 patients, failed aortic valves in 153 patients, and failed aortic and mitral valves in 28 patients. Including 26 operations (6%) for acute endocarditis, 153 operations (38%) were nonelective. One hundred nine patients (27%) had other valves repaired or replaced, and 72 (18%) had coronary bypass grafting. The incidence of death in the mitral, aortic, and double-valve groups was respectively, 15 (6.8%), 12 (7.8%), and 4 (14.3%); and the incidence of prolonged postoperative hospital stay (14 days) was, respectively, 57 (26.0%), 41 (26.8%), and 8 (28.6%). Only 7 of 147 patients (4.8%) having elective, isolated, first-time valve reoperation died. Multivariable predictors (p0.05) of hospital death were age greater than 65 years, male sex, renal insufficiency, and nonelective operation; and predictors of prolonged stay were acute endocarditis, renal insufficiency, any concurrent cardiac operation, and elevated pulmonary artery systolic pressure.Reoperative bioprosthetic valve replacement can be performed with acceptable mortality and hospital stay. The best results are achieved with elective valve replacement, without concurrent cardiac procedures.