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Biomedical subjects

L H Cohn

Publications and source records attributed to L H Cohn.

At least 109 records · Page 6Linked to original sources

Long-term results of mitral valve reconstruction for regurgitation of the myxomatous mitral valve.

The myxomatous, degenerated, prolapsed or "floppy" mitral valve is the most common cause of mitral regurgitation in North America. Mitral valve reconstruction for mitral regurgitation was carried out in 219 consecutive patients with a myxomatous mitral valve from 1984 to 1993. Of the 139 men and 80 women, 23 to 84 years of age (mean 63 years), 36% of patients were 70 years of age or older, 77% were in New York Heart Association functional class III or IV, and 29% had coronary artery disease necessitating coronary bypass. The most common operation was posterior leaflet resection (161 patients [73%]). The anterior leaflet was resected in 14 patients, and both the anterior and posterior leaflets were resected in 15 patients. A variety of other techniques were used, including commissuroplasty and use of annuloplasty rings. A flexible Duran ring was used in 111 patients (51%), a Carpentier-Edwards ring in 44 patients (20%), and no ring was used in 64 patients (29%). Five operative deaths occurred (2.3%); four of the five deaths occurred in patients 70 years of age or older (5.1%); and one in 141 patients (0.7%) was younger than 70 years of age. In the late postoperative period (mean follow-up 2 years), 90% of patients had no symptoms, two had endocarditis, and seven patients had thromboemboli (transient in four, permanent in three). Structural valve degeneration requiring reoperation occurred late in 12 patients; eight were in posterior leaflet resection and two in anterior or anterior and posterior; six of 12 had no annuloplasty ring. The incidence of structural valve degeneration was less than 5% from 1990 to 1993. No systolic anterior motion of the mitral valve was seen with postoperative echocardiography before discharge. Actuarial analysis at 5 years for overall survival was 86% +/- 5%, freedom from infectious valve degeneration 97% +/- 2%, and freedom from thromboembolism 94% +/- 3%. Freedom from structural valve degeneration overall was 83% +/- 4%, with a flexible ring it was 89% +/- 6%, with a rigid ring it was 88% +/- 6%, and with no ring it was 67% +/- 12% (p = 0.03). Mitral valve reconstruction for complicated myxomatous disease of the mitral valve, regardless of leaflet involvement, is feasible and offers excellent early and late results.

Actuarial Analysis↗

Intraoperative myocardial ischemia detection with laser-induced fluorescence.

Myocardial ischemia can be detected at the mitochondrial level by measuring shifts in nicotinamide adenine dinucleotide and its reduced form. Using a pulsed nitrogen laser and an optical multichannel analyzer, we monitored myocardial metabolism by measuring laser-induced nicotinamide adenine dinucleotide (reduced form) fluorescence in a large animal model of acute ischemia. Eight opened-chest sheep underwent occlusion of branches of the left anterior descending coronary artery, establishing a 15% infarct of the left ventricle. For the simulation of the clinical scenario, after 60 minutes of occlusion, the animals were supported by cardiopulmonary bypass, the aorta was crossclamped, and cold crystalloid cardioplegic solution was administered. The occlusion was removed after 10 minutes, and two additional doses of cardioplegic solution were delivered at 10-minute intervals. The aortic crossclamp was released, and a 30-minute period of reperfusion on bypass ensued. The hearts were then weaned off bypass and allowed to recover. Laser-induced fluorescence was measured inside, outside, and along the border of the infarct. Baseline measurements were made before occlusion, immediately after occlusion, and then at 5, 10, and 20 minutes after occlusion. The results show that immediately after occlusion there is a 200% +/- 30% (mean +/- standard deviation) increase in laser-induced fluorescence in the infarct zone, a 110% +/- 30% increase along the border, and no significant change in the area outside the infarct. The fluorescence in the infarct reaches a plateau in 5 minutes at 270% +/- 30%, whereas along the border it reaches a peak near end ischemia of 110% +/- 40%. With the first dose of cardioplegic solution, fluorescence increases outside the infarct and decreases inside the infarct and along the border to 120% +/- 30%, where it remains for all areas until the aortic crossclamp is removed. Fluorescence then drops to 70% +/- 20% and finally returns to baseline after 5 minutes of recovery. All of these shifts in laser-induced fluorescence were statistically significant (p < 0.01). The changes noted with doses of cardioplegic solution reflect the hypothermic and hyperkalemic effects on the myocardium. Laser-induced fluorescence provides a sensitive and specific method of monitoring myocardial ischemia during the operation. It also provides instantaneous feedback of metabolic changes that may be useful in evaluating the effects of different cardioplegic regimens and in monitoring reperfusion injury.

Animals↗

Prevention of CD18-mediated reperfusion injury enhances the efficacy of UW solution for 15-hr heart preservation.

University of Wisconsin solution (UW) has been demonstrated to improve donor heart preservation. During reperfusion, however, myocardial performance may still remain limited by neutrophil (PMN)-mediated injury, manifested by the "low-reflow" phenomenon and myocardial "stunning." Since PMN adhesion is an important mechanism of PMN-mediated injury, we tested whether blocking PMN adhesion molecule CD18 would enhance the efficacy of UW for 15-hr heart preservation. Rabbit hearts (n = 15) were arrested with, and preserved for 15 hr in, 4 degrees C UW. After insertion of an left ventricular (LV) balloon, hearts were heterotopically transplanted into recipients pretreated with either intravenous (i.v.) saline (vehicle, n = 8) or i.v. anti-CD18 monoclonal antibody R15.7 (anti-CD18, n = 7). After 1 hr reperfusion the slope of the peak systolic pressure-volume (P-V) relation (Emax), the exponential coefficient (beta), the volume-axis intercept (Vo) of the end-diastolic P-V relation, and the time constant of the exponential LV pressure decay after dP/dt min (tau) were measured. Blood flow was measured with microspheres from which coronary vascular resistance (CVR) was calculated. Tissue %H2O was also measured. Between groups there were no significant differences in Emax (70.5 +/- 6.1 vs 63.7 +/- 6.0 mm Hg/ml, P > 0.05), beta (3.3 +/- 0.5 vs 4.3 +/- 0.5, P > 0.05), Vo (-0.4 +/- 0.1 vs -0.4 +/- 0.2 ml, P > 0.05) or %H2O (81.3 +/- 1.1 vs 80.0 +/- 0.9, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Decrease in operative risk of reoperative valve surgery.

We analyzed the risk of valve re-replacement in 640 patients reoperated on between 1980 and 1992. This represented 17% of total valve operations (640/3,764) during that period. A univariate and logistic multivariate analysis was carried out for four sequential periods for the 640 re-replacement patients to determine if changing methods of perfusion and myocardial protection affected recent results. There were 323 female and 317 male patients with a mean age of 58 years (range, 17 to 84 years). Ninety-seven (15%) had coronary artery bypass grafting, 135 (21%) were 70 years old or older, 377 (59%) were in New York Heart Association functional class III or less, and 263 (41%) were in functional class IV. The aortic valve was re-replaced in 245, the mitral valve in 289, and both aortic and mitral synchronously in 106. Four periods were analyzed: 1980 through 1982, 1983 through 1985, 1986 through 1988, and 1989 through 1992. The overall operative mortality was 65 of 640 patients (10%), falling from 12/73 (16%) in 1980 through 1982 to 23/268 (8%) in 1989 through 1992 (p = 0.05). Univariate and multivariate logistic analysis documented that New York Heart Association functional class was highly significant for operative mortality; operative mortality was 4% for functional classes I through III, and 19% for functional class IV (p < or = 0.001). The requirement for coronary bypass was of borderline significance (p = 0.05), and year of operation was also significant. Mortality for re-replacement of aortic valve fell from 15% to 10%, double valve from 20% to 9%, and mitral valve from 16% to 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Femoral veno-arterial extracorporeal life support with minimal or no heparin.

Recent technological advances in cardiopulmonary bypass circuits achieving surface bonding with heparin have permitted prolonged extracorporeal life support (ECLS) in experimental studies without the use of systemic anticoagulation. Excessive bleeding and the need for massive transfusions after extended ECLS with systemic heparinization have often led to the development of sepsis and multisystem organ failure. The Carmeda bioactive surface circuit, along with a Bio-Medicus centrifugal pump (Bio-Pump) and the femoral veno-arterial route, were used successfully in 3 patients requiring ECLS between April 1992 and December 1992. In 2 patients the need for ECLS was acute allograft dysfunction after orthotopic cardiac transplantation with no evidence of cellular rejection. Both patients were receiving multiple inotropes and intraaortic balloon counter-pulsation; their condition continued to deteriorate rapidly before the initiation of ECLS. The third patient failed to be weaned from cardiopulmonary bypass after myocardial revascularization for ischemic cardiomyopathy. Time on ECLS ranged from 57 to 128 hours. No systemic anticoagulation was used. One patient received no heparin, and the other 2 patients received intermittent heparin infusion to maintain an average activated clotting time of 195 and 214 seconds. Multisystem organ dysfunction present before initiation of ECLS was rapidly reversed, and all patients were weaned successfully without any immediate major complications. The ability to conduct prolonged ECLS without systemic anticoagulation and without repeat sternotomy opens new avenues for the use of this procedure in profound heart failure.

Blood Coagulation↗

The first successful surgical treatment of mitral stenosis: the 70th anniversary of Elliot Cutler's mitral commissurotomy.

In 1923 Elliot Carr Cutler, in conjunction with his cardiology colleague, Samuel Levine, performed a closed transventricular mitral commissurotomy with a tenotomy knife on a 12-year-old patient dying of rheumatic mitral stenosis at the Peter Bent Brigham Hospital. This operation was carried out after several years of experimentation regarding resuscitation of the heart, appropriate incisions, and the pathophysiology of mitral stenosis. The interest in mitral stenosis was rampant at the time because of the huge number of patients suffering from this public health problem. The patient survived and went on to die of pneumonia 4 years postoperatively. Subsequent to this, Cutler performed seven more operations using his new cardiovalvulotome, which was to create controlled mitral regurgitation. Unfortunately, this concept did not promote long-term success and a moratorium for these operations was called in 1929. Nevertheless, this pioneering effort in 1923 was the first successful operation to treat valvular heart disease by a surgical technique.

Child↗

Leukotrienes D4 and E4 produced in myocardium impair coronary flow and ventricular function after two hours of global ischaemia in rat heart.

OBJECTIVE: Leukotrienes D4 and E4 are potent coronary vasoconstrictors and myocardial depressants. The aim was to investigate the contribution of myocardial leukotrienes to impairment of coronary flow and recovery of contractile function in rat hearts subjected to 2 h of global ischaemia. METHODS: Rat hearts were mounted on a working Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solution at 37 degrees C for 30 min. Hearts were then arrested with either standard potassium crystalloid cardioplegic solution (n = 6), or with cardioplegic solution containing the leukotriene D4, E4 receptor antagonist Ly171883 (n = 6). Arrested hearts were maintained at 15 degrees C for 2 h, then rewarmed to 37 degrees C during 30 min working reperfusion. Coronary effluent was analysed by radioimmunoassay for leukotriene C4, D4, E4, and F4 levels. Immediately prior to cardiac arrest, and again after 30 min reperfusion, coronary flow, and aortic outflow and pressure were measured. RESULTS: Postischaemic leukotriene levels were increased compared to preischaemic levels in both groups [pooled measurements: 133.3 (SD 136.4) v 20.7(17.8) pg.0.1 ml-1, p < 0.05]. Postischaemic coronary vascular resistance was increased by 80% in controls (p < 0.001) compared to 19% (p = NS) in treated hearts. In addition, functional recovery was significantly greater in treated hearts compared to controls [82(3)% v 53(3)% for coronary flow; 79(3)% v 50(2)% for cardiac output; 82(4)% v 54(3)% for stroke work]. CONCLUSIONS: Leukotrienes are endogenously produced by the heart, and this production is significantly increased after global ischaemia and reperfusion. Reversal of significantly increased coronary vascular resistance coupled with improved functional recovery in hearts treated with LY171883 demonstrates an important contribution of endogenously produced leukotrienes to coronary vascular impairment and functional stunning of the globally ischaemic, reperfused heart.

Acetophenones↗

Myocardial stunning and reperfusion injury in cardiac surgery.

This article reviews the evidence that myocardial stunning during surgical reperfusion after coronary revascularization or heart transplantation is not strictly due to myocardial injury sustained during ischemia, but results from pathophysiological events triggered by reperfusion (reperfusion injury). In sheep, left ventricular (LV) dP/dt and stroke work were reduced up to 50%, and 60% to 70% necrosis was observed in the area at risk during 3 hours reperfusion following coronary occlusion and cardioplegic arrest on bypass. Reperfusion with leukocyte depleted blood, or pharmacological blockade of either thromboxane or leukotriene receptors, provided significant improvements in LV function and myocardial blood flow, with a 40% to 50% reduction in necrosis. Similar results have been obtained using animal heart subjected to 2 to 3 hours arrest at either 4 degrees C or 15 degrees C, simulating cardiac preservation and reperfusion after transplantation. Diastolic pressure was significantly elevated, and increases in the time constant for relaxation of LV pressure and coronary vascular resistance were noted. These indices of myocardial stunning were reversed after blocking neutrophil-endothelial cell interaction with monoclonal antibodies against CD18 or ICAM-1 receptors, and significant improvements were also obtained after either thromboxane or leukotriene receptor blockade. We conclude that immediate postoperative myocardial stunning results largely from reperfusion injury that occurs due to an acute inflammatory response to ischemia and reperfusion, and that stunning can be largely reversed with appropriate pharmacological intervention.

Animals↗

Aortic valve replacement in the elderly. Effect of gender and coronary artery disease on operative mortality.

BACKGROUND: Aortic valve replacement remains the treatment of choice for aortic valve disease, even in the extreme elderly who may present with advanced symptoms. Defining risk factors for short-term survival was the object of this study. METHODS AND RESULTS: This was a retrospective analysis of 717 patients at least 70 years of age who underwent aortic valve replacement alone or with coronary artery bypass graft between 1980 and 1992. Age range was 70 to 95 years, and mean age was 77 years; there were 529 septuagenarians (74%); 188 were octogenarians (26%); 326 were women (45%); and 386 patients (54%) had aortic valve replacement and coronary artery bypass graft. Atrial fibrillation/flutter or heart block was present in 16%, and 34% of patients were in New York Heart Association (NYHA) functional class IV. Aortic stenosis was present in 88%, and mechanical prostheses were used in 22% of patients. There were 47 deaths, giving an overall operative mortality of 6.6%, with 4.2% for aortic valve replacement and 8.8% for aortic valve replacement and coronary artery bypass graft (P = .01). The operative mortality for aortic valve replacement was 2.9% versus 10.3% for aortic valve replacement and coronary artery bypass graft in women (P = .006). The corresponding values for men were 5.6% and 7.4% (P = .31). Multivariate logistic regression showed coronary artery bypass graft and NYHA class IV to be significant predictors of operative mortality in women. The significant predictors in men were NYHA class IV, atrial fibrillation/flutter or heart block rhythm, and the use of mechanical prosthesis. Age was not a predictor of operative mortality in either sex. CONCLUSIONS: Aortic valve replacement carries an acceptable mortality rate in elderly patients. Female gender was a significant predictor of operative mortality in the concomitant coronary artery bypass graft group; however, gender was not a predictor of operative mortality in the isolated aortic valve replacement group. Advance stage of the disease process represented by NYHA class IV was a significant predictor of mortality for the whole group, stressing the need for earlier referral for surgery.

Aged↗

Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury?

After crystalloid cardioplegic arrest, cardiac-derived thromboxane A2 may be an important initiating mediator of no-reflow and hemodynamic deterioration during reperfusion because of its potent vasoactive properties. Although previous studies have already documented the increased release of cardiac thromboxane A2 after ischemia, none have studied the effects of cardiac thromboxane A2 on hemodynamics. We therefore tested the ability of cardiac thromboxane A2 to mediate deterioration of coronary flow and functional recovery during reperfusion after global ischemia. Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548. In eight of 15 hearts in each group, preischemic and postischemic aortic flow, coronary flow, cardiac output, heart rate, and stroke work were determined. In the remaining seven hearts in each group, preischemic and postischemic coronary effluent levels of the stable hydrolysis product of thromboxane A2 and thromboxane B2 were determined with radioimmunoassay through the use of nonrecirculating perfusate. At the completion of the experiment, water content was determined by wet weight/dry weight calculations. In a separate group (n = 7) preischemic myocardial water content was determined. Within the group protected by cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly decreased (p < 0.05) compared with preischemic values (aortic flow, 50.8 +/- 2.7 versus 29.4 +/- 3.3 ml/min; coronary flow, 13.2 +/- 1.3 versus 8.5 +/- 1.3 ml/min; cardiac output, 64.0 +/- 3.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.5 +/- 0.7 versus 7.1 +/- 0.8 cm H2O.ml). In relation to the group with cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly greater (p < 0.05) in the group with the receptor antagonist (aortic flow: 49.5 +/- 2.4 versus 29.4 +/- 3.3 ml/min; coronary flow; 12.4 +/- 1.2 versus 8.5 +/- 1.3 ml/min; cardiac output, 62.0 +/- 2.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.6 +/- 0.8 versus 7.1 +/- 0.8 cm H2O.ml). Overall, postischemic coronary effluent thromboxane B2 levels were greater than preischemic values (105.6 +/- 12.4 versus 69.6 +/- 9.8, p < 0.05) and treatment with the receptor antagonist did not significantly affect postischemic thromboxane B2 levels (92.0 +/- 7.3 versus 82.3 +/- 15.5, p = not significant). Neither ischemia nor treatment with the receptor antagonist significantly affected heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Myocardial protection for reoperative cardiac surgery in acquired heart disease.

We have reviewed a variety of techniques that have recently been used to improve the results of reoperation coronary bypass valve re-replacement and redo thoracic aortic surgery. The basic tenets of management in these high-risk areas are: (1) innovative use of cardiopulmonary bypass techniques to improve patient safety, including deep hypothermic arrest, (2) use of retrograde as well as antegrade infusion of cardioplegic solutions, (3) meticulous operative technique, (4) prevention of left ventricle distension, (5) TEE monitoring of intracardiac air, and (6) careful post-bypass hemodynamic monitoring. Reoperative CABG specifically requires avoiding injury to previously placed open conduits or atherosclerotic conduits, an increasingly recognized risk factor in these patients. Though direct myocardial cardioplegic protective techniques are very important for reducing operative risk, the importance of the total operative plan is critical for maximizing patient safety and ensuring improved long-term survival.

Aortic Aneurysm, Thoracic↗

Surgical treatment of adult atrial septal defect: early and long-term results.

OBJECTIVES: The purpose of this study is to determine the early and late results of the surgical repair of atrial septal defect in adults. BACKGROUND: Progressively limiting, untreated atrial septal defect can lead to the early death of middle-aged adults. Recently it has been suggested that the closure of atrial septal defects might be accomplished with interventional cardiac techniques. Although the long-term results of the transcatheter closure are as yet unknown, the outcome of surgical therapy has been shown to be beneficial for almost 40 years. METHODS: Between 1971 and 1991, 166 consecutive patients underwent surgical repair of a secundum or sinus venosus atrial septal defect, or both, at the Brigham and Women's Hospital, Boston. There were 120 women and 46 men in this group; the mean age was 44 years and 58 (35%) of the patients were > or = 50 years old. The average pulmonary to systemic flow ratio was 3.0, and 57 patients had a peak systolic pulmonary artery pressure > 30 mm Hg. RESULTS: There were two operative deaths (early mortality rate 1.2%), and 13% of the patients had a perioperative complication. One hundred fifty-three of the 164 survivors were followed up for a mean of 90 months (range 2 to 247). There were eight late deaths (late mortality rate 4.9%) and a late morbidity rate of 12.4% (in most cases due to arrhythmias). The 5- and 10-year survival rates are 98% and 94%, respectively, and the probability of event-free survival (with no morbidity or mortality) at 5 years is 97% and at 10 years is 92%. CONCLUSIONS: The results indicate that the surgical correction of atrial septal defect in adults is safe and efficacious as confirmed by 20 years of follow-up.

Adult↗

Long-term follow-up of patients undergoing myotomy/myectomy for obstructive hypertrophic cardiomyopathy.

The long-term results of patients undergoing myotomy/myectomy of the ventricular septum for obstructive hypertrophic cardiomyopathy are documented in 31 patients (15 women, 16 men, age range 21 to 80 years [mean 55]) with mean New York Heart Association functional class III to IV congestive heart failure, who underwent radical myotomy/myectomy at the Brigham and Women's Hospital from 1972 to 1991. Preoperative gradients by catheterization or echocardiography ranged from 26 to 240 mm Hg (average 96). There were no operative deaths. Two patients developed early postoperative complete heart block requiring a transvenous pacemaker. Clinical follow-up was 1 to 14 years (mean 6.5). All surviving patients were restudied by echocardiography and clinical examination. The mean postoperative functional class was II. Postoperative gradients ranged from 0 to 30 mm Hg (mean 4.5) (p less than 0.001 compared with preoperative values). There were 5 late deaths (low cardiac output in 2, stroke in 2, and acute respiratory failure in 1); 4 of 5 deaths occurred in patients with concomitant coronary artery disease. Survival at 10 years was 86 +/- 9%. There were no reoperations for subaortic obstruction.

Cardiomyopathy, Hypertrophic↗

Combined carotid and coronary revascularization: the preferred approach to the severe vasculopath.

The timing of carotid endarterectomy (CEA) and coronary revascularization (CABG) for concomitant disease is controversial. Results of combined CEA/CABG in 127 patients (age range, 46 to 82 years; mean age, 65 years; 61% male) from 1978 to 1991 were reviewed. Ninety-five patients (75%) were in New York Heart Association functional class III or IV, 48 (38%) had left main coronary artery disease, and 32 (28%) had depressed ejection fraction ( < 0.50). Forty (32%) had asymptomatic bruits, 61 (48%) transient ischemic attacks, and 26 (20%) prior strokes. Seventy-five (59%) had bilateral carotid stenosis, including 20 (16%) with contralateral occlusions. Perioperative mortality was 7 of 127 (5.5%), and all deaths were cardiac related. Myocardial infarctions occurred in 6 of 127 patients (4.7%) and were nonfatal in 3 (2.3%). Permanent strokes occurred in 7 of 127 (5.5%) and were ipsilateral in 5 (3.9%). Perioperative stroke did not occur in the asymptomatic group, but the risk was higher in those with prior stroke (19%) or with contralateral carotid occlusion (15%). The stroke risk for our patients with carotid disease having CABG without CEA is not known, but the literature reports rates as high as 14%. For our patients without known concomitant disease, the risk of permanent stroke was 1.0% (31/3012) for isolated CABG and 1.5% (7/482) for isolated CEA. The late results after CEA/CABG revealed a 5-year survival of 70% +/- 5%, which correlated with ejection fraction ( > or = 0.50, 81% +/- 5%; < 0.50, 45% +/- 11%; p < 0.003). Freedom from late permanent ipsilateral stroke was 97% +/- 2% at 8 years. Freedom from stroke at 5 years was lower among patients with a previous stroke (71% +/- 10%) compared with transiently symptomatic (90% +/- 4%) and asymptomatic (96% +/- 4%) patients (p < 0.03). Combined CEA/CABG is a useful option in this high-risk group of patients with extensive atherosclerosis; avoids a subsequent hospitalization, anesthetic, and delay period; and provides long-term protection from ipsilateral stroke.

Actuarial Analysis↗

Optimal approach to the mitral valve: dissection of the interatrial groove.

Surgical exposure of the mitral valve has challenged surgeons for more than 30 years. Many ingenious, but often complex approaches have been devised during this time. Using the dissection of the interatrial groove to bring the left atrial incision more anterior and medial, we have achieved excellent exposure in more than 300 mitral valve procedures. This simple technique does not lengthen the procedure and is not associated with an increased risk of either early or late morbidity.

Boston↗