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Background: Quantification of left atrial (LA) conduit function and its contribution to left ventricular (LV) filling is challenging because it requires simultaneous measurements of both LA and LV volumes. The functional relationship between LA conduit function and the severity of diastolic dysfunction remains controversial. We studied the role of LA conduit function in maintaining LV filling in advanced diastolic dysfunction., Methods: We performed volumetric and flow analyses of LA function across the spectrum of LV diastolic dysfunction, derived from a set of consecutive patients undergoing multiphasic cardiac computed tomography scanning (n=489). From LA and LV time-volume curves, we calculated 3 volumetric components: (1) early passive emptying volume; (2) late active (booster) volume; and (3) conduit volume. Results were prospectively validated on a group of patients with severe aortic stenosis (n=110)., Results: The early passive filling progressively decreased with worsening diastolic function ( P <0.001). The atrial booster contribution to stroke volume modestly increases with impaired relaxation ( P =0.021) and declines with more advanced diastolic function ( P <0.001), thus failing to compensate for the reduction in early filling. The conduit volume increased progressively ( P <0.001), accounting for 75% of stroke volume (interquartile range, 63-81%) with a restrictive filling pattern, compensating for the reduction in both early and booster functions. Similar results were obtained in patients with severe aortic stenosis. The pulmonary artery systolic pressure increased in a near-linear fashion when the conduit contribution to stroke volume increased above 60%. Maximal conduit flow rate strongly correlated with mitral E-wave velocity (r=0.71; P <0.0001), indicating that the increase in mitral E wave in diastolic dysfunction represents the increased conduit flow., Conclusions: An increase in conduit volume contribution to stroke volume represents a compensatory mechanism to maintain LV filling in advanced diastolic dysfunction. The increase in conduit volume despite increasing LV diastolic pressures is accomplished by an increase in pulmonary venous pressure., Competing Interests: Disclosures None.

Background: Electroporation is a promising nonthermal ablation method for cardiac arrhythmia treatment. Although initial clinical studies found electroporation pulsed-field ablation (PFA) both safe and efficacious, there are significant knowledge gaps concerning the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation, contributed by the paucity of suitable human in vitro models. Here, we aimed to establish and characterize a functional in vitro model based on human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue, and to study the fundamentals of cardiac PFA., Methods: hiPSC-derived cardiomyocytes were seeded as circular cell sheets and subjected to different PFA protocols. Detailed optical mapping, cellular, and molecular characterizations were performed to study PFA mechanisms and electrophysiological outcomes., Results: PFA generated electrically silenced lesions within the hiPSC-derived cardiac circular cell sheets, resulting in areas of conduction block. Both reversible and irreversible electroporation components were identified. Significant electroporation reversibility was documented within 5 to 15-minutes post-PFA. Irreversibly electroporated regions persisted at 24-hours post-PFA. Per single pulse, high-frequency PFA was less efficacious than standard (monophasic) PFA, whereas increasing pulse-number augmented lesion size and diminished reversible electroporation. PFA augmentation could also be achieved by increasing extracellular Ca 2+ levels. Flow-cytometry experiments revealed that regulated cell death played an important role following PFA. Assessing for PFA antiarrhythmic properties, sustainable lines of conduction block could be generated using PFA, which could either terminate or isolate arrhythmic activity in the hiPSC-derived cardiac circular cell sheets., Conclusions: Cardiac electroporation may be studied using hiPSC-derived cardiac tissue, providing novel insights into PFA temporal and electrophysiological characteristics, facilitating electroporation protocol optimization, screening for potential PFA-sensitizers, and investigating the mechanistic nature of PFA antiarrhythmic properties., Competing Interests: Disclosures None.

Background: Current treatment of fluid retention in heart failure relies primarily on diuretics. However, adequate decongestion is not achieved in many patients. We aimed to study the feasibility and short-term performance of a novel approach to remove fluids and sodium directly from the interstitial compartment by enhancing sweat rate., Methods: We used a device designed to enhance fluid and salt loss via the eccrine sweat glands. Skin temperature in the lower body was increased from 35 °C to 38 °C, where the slope of the relationship between temperature and sweat production is linear. The sweat evaporates instantaneously, thus avoiding the awareness of perspiration. The primary efficacy endpoint was the ability to increase skin temperature to the desired range. A secondary efficacy endpoint was a clinically meaningful hourly sweat output, defined as ≥150 mL/h. The primary safety endpoint was any procedure-related adverse events., Results: We studied 6 normal subjects and 18 patients with congestion. Participants underwent 3 treatment sessions of up to 4 hours. Skin temperature increased to a median of 37.5 °C (interquartile range, 37.1-37.9 °C) with the median core temperature increasing by 0.2 °C (interquartile range, 0.1-0.3 °C). The median hourly weight loss during treatment was 215 g/h (interquartile range, 165-285; range, 100-344 g/h). In 80% of treatment procedures, the average sweat rate was ≥150 mL/h. There were no significant changes in hemodynamic variables or renal function and no procedure-related adverse events., Conclusions: Enhancing sweat rate was safe and resulted in a clinically meaningful fluid removal and weight loss., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04578353.

Objectives: Hypertrophic cardiomyopathy (HCM) is characterized by diastolic dysfunction, which is difficult to assess by noninvasive methods. We hypothesized that measurement of simultaneous left ventricular (LV) and left atrial (LA) volume changes by cardiac computed tomography would be useful in the assessment of diastolic function in HCM., Methods: We studied 21 patients with HCM and 21 age-matched controls. The LA and LV volumes were calculated and early and late diastolic volume changes derived., Results: The HCM patients had significantly larger LA volumes and reduced LA total emptying fraction (30 ± 7% vs 42 ± 6%; P < 0.0001). Conduit volume was increased (30 ± 6 vs 22 ± 4 mL/m; P < 0.0001) and contributed a significantly higher proportion of total LV diastolic filling, suggesting that passive filling of the LV compensates for LA dysfunction, but at the expense of increased pulmonary filling pressure., Conclusions: This study suggests that simultaneous depiction of computed tomography-derived LV and LA volume changes can characterize diastolic dysfunction in HCM.

Rapid reperfusion is crucial to reduce mortality in patients with ST elevation myocardial infarction. Prehospital patient delay, defined as time from symptoms onset to the decision to seek medical attention, accounts for a large proportion of cases with delayed reperfusion. However, whether pain modulation processes are involved in this phenomenon is not known. We hypothesized that prehospital patient delay may be affected by a reduction of perceived pain perception and pain modulation pattern. Pain threshold, magnitude estimation of suprathreshold stimulation, mechanical temporal summation and conditioned pain modulation (CPM), and recalls of pain magnitude at the onset of chest pain were obtained in 67 patients with first ST elevation myocardial infarction. The study's primary outcome was prehospital patient delay. The median patient delay was 24 (interquartile range, 0.5-72) hours. Of all psychophysical pain measures including pain threshold, magnitude estimation of suprathreshold stimulation, mechanical temporal summation, as well as CPM, only warm sensation threshold was independently associated with lower clinical chest pain intensity (P = 0.01). Multivariable regression analysis (R = 0.449; P < 0.0001) revealed an inverse independent association between chest pain intensity (P < 0.001) and patient delay, whereas efficient CPM was positively associated with prolonged patient delay (P = 0.034). The electrocardiography-derived myocardial ischemic area was not associated with chest pain intensity or patient delay, indicating that the affected ischemic tissue is not a dominant component that determines pain response. In conclusion, beyond the perceived chest pain intensity, the activation pattern of descending inhibition pathways during coronary occlusion affects pain interpretation and behavior during acute coronary occlusion.

Objective: Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages., Methods and Results: Highly purified heparanase was added to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like receptor-4 knockout mice were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction, stable angina, and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with stable angina or acute myocardial infarction. Addition or overexpression of heparanase variants resulted in marked increase in tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll-like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute myocardial infarction, compared with patients with stable angina and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared with specimens of stable plaque and controls., Conclusions: Heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability.

Background: Dyspnea relief constitutes a major treatment goal and a key measure of treatment efficacy in decompensated heart failure. However, there are no data with regard to the relationship between hemodynamic measurements during treatment and dyspnea improvement., Methods and Results: We studied 233 patients assigned to right heart catheterization in the Vasodilation in the Management of Acute Congestive Heart Failure trial. Dyspnea (assessed using a 7-point Likert scale) and hemodynamic parameters were measured simultaneously at 15 and 30 minutes and 1, 2, 3, 6, and 24 hours. Dyspnea relief was defined as moderate or marked improvement. There was a time-dependent association between the reductions in pulmonary capillary wedge pressure (PCWP; 25.4, 24.6, 24.0, 23.5, 23.4, 21.5, and 19.9 mm Hg) and the percentage of patients achieving dyspnea relief (17.7%, 24.6%, 32.2%, 36.2%, 37.8%, 47.4%, and 66.1%, in the respective time points). Multivariable logistic generalized estimating equations modeling demonstrated that reductions of both PCWP and mean pulmonary artery pressure were independently associated with dyspnea relief. Compared with the highest PCWP quartile, the adjusted odds ratios for dyspnea relief were 0.92 (95% confidence interval [CI], 0.67-1.29), 1.07 (95% CI, 0.75-1.55), and 1.80 (95% CI, 1.22-2.65) in the third, second, and first PCWP quartiles, respectively (P(trend)=0.003). Compared with the highest mean pulmonary artery pressure quartile, the adjusted odds ratios for dyspnea relief were 2.0 (95% CI, 1.41-2.82), 2.23 (95% CI, 1.52-3.27), and 2.98 (95% CI, 1.91-4.66) in the third, second, and first mean pulmonary artery pressure quartiles, respectively (P(trend)<0.0001)., Conclusions: A clinically significant improvement in dyspnea is associated with a reduction in both PCWP and mean pulmonary artery pressure.

Background: In patients with heart failure, pulmonary hypertension (PH) predicts higher risk for morbidity and mortality. However, few data are available on the prognostic implications of reactive (precapillary) PH superimposed on passive (postcapillary) PH., Methods and Results: We performed a subgroup analysis of 242 patients with acute decompensated heart failure assigned to pulmonary artery catheter placement in the Vasodilation in the Management of Acute Congestive Heart Failure trial. Patients were classified into 3 groups, using the final (posttreatment) hemodynamic measurements: (1) no PH (mean pulmonary artery pressure ≤ 25 mm Hg; (2) passive PH (mean pulmonary artery pressure > 25, pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance ≤ [corrected] Wood units); and (3) reactive PH (mean pulmonary artery pressure > 25, [corrected] pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance > 3 Wood units). Fifty-eight patients were classified as normal mean pulmonary artery pressure, 124 with passive PH and 60 with reactive PH. During follow-up of 6 months, 5 (8.6%), 27 (21.8%), and 29 (48.3%) deaths occurred in patients without PH, patients with passive PH, and with reactive PH, respectively (P<0.0001). After multivariable adjustments, reactive PH remained an independent predictor of death, with an adjusted hazard ratio of 4.8 compared with patients without PH, and 2.8 compared with patients with passive PH (95% confidence interval, 1.7 to 4.7, P=0.0001). Similar results were obtained when reactive PH was defined on the basis of transpulmonary gradient., Conclusions: Reactive PH is common among patients with acute decompensated heart failure after initial diuretic and vasodilator therapy. The adverse outcome associated with PH is predominantly due to increased mortality rates in the subgroup of patients with reactive PH.

Background: Diabetes is often associated with an abnormal diastolic function. However, there are no data regarding the contribution of diastolic dysfunction to the development of heart failure (HF) in diabetic patients after acute myocardial infarction., Methods and Results: A total of 1513 patients with acute myocardial infarction (417 diabetic) underwent echocardiographic examination during the index hospitalization. Severe diastolic dysfunction was defined as a restrictive filling pattern (RFP) based on E/A ratio >1.5 or deceleration time <130 ms. The primary end points of the study were readmission for HF and all-cause mortality. The frequency of RFP was higher in patients with diabetes (20 versus 14%; P=0.005). During a median follow-up of 17 months (range, 8 to 39 months), 52 (12.5%) and 62 (5.7%) HF events occurred in patients with and without diabetes, respectively (P<0.001). There was a significant interaction between diabetes and RFP (P=0.04) such that HF events among diabetic patients occurred mainly in those with RFP. The adjusted hazard ratio for HF was 2.77 (95%, CI 1.41 to 5.46) in diabetic patients with RFP and 1.21 (95% CI, 0.75 to 1.55) in diabetic patients without RFP. A borderline interaction (P=0.059) was present with regard to mortality (adjusted hazard ratio, 3.39 [95% CI, 1.57 to 7.34] versus 1.61 [95% CI, 1.04 to 2.51] in diabetic patients with and without RFP, respectively)., Conclusions: Severe diastolic dysfunction is more common among diabetic patients after acute myocardial infarction and portends adverse outcome. HF and mortality in diabetic patients occur predominantly in those with concomitant RFP.

Objective: To evaluate indications, findings, therapies, safety, and technical success of endoscopic retrograde cholangiopancreatography (ERCP) in children of the Emma Children's Hospital Academic Medical Centre in Amsterdam, the Netherlands., Design: Descriptive. Retrospective analysis by medical records., Patients and Methods: Information was obtained by chart review of patients between 0 and 18 years who underwent ERCP from 1995 to 2005 in our center. The following data were analyzed: indications, findings, therapies, safety, and technical success. Success was defined as obtaining accurate diagnostic information or succeeding in endoscopic therapy., Results: Sixty-one children (age 3 days to 16.9 years, mean age 7.0 years) underwent a total of 99 ERCPs. Of those patients, 51% (31/61) were younger than 1 year, 84% had biliary indications, and 16% had pancreatic indications for the performance of ERCP. The complication rate was 4% (4/99) and included substantial pancreatitis and mild irritated pancreas. No complications occurred in children younger than 1 year., Conclusions: ERCP is a safe and valuable procedure for children of all ages with suspicion of pancreaticobiliary diseases. Indications for ERCP are different for children and adults. A laparotomy could be prevented in 12% of children with suspicion of biliary atresia. Further research is required to determine the role of MRCP versus ERCP.

Objective: Clinical trials of vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major antioxidant protein, is a determinant of cardiovascular events in patients with Type 2 diabetes mellitus (DM). The Hp gene is polymorphic with 2 common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior antioxidant protection compared with the Hp 1 allelic product. We sought to test the hypothesis that vitamin E could reduce cardiovascular events in DM individuals with the Hp 2-2 genotype, a subgroup that comprises 2% to 3% of the general population., Methods and Results: 1434 DM individuals > or = 55 years of age with the Hp 2-2 genotype were randomized to vitamin E (400 U/d) or placebo. The primary composite outcome was myocardial infarction, stroke, and cardiovascular death. At the first evaluation of events, 18 months after initiating the study, the primary outcome was significantly reduced in individuals receiving vitamin E (2.2%) compared with placebo (4.7%; P=0.01) and led to early termination of the study., Conclusions: Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2-2 genotype (ClinicalTrials.gov NCT00220831).

Background: The lack of pain alarm in painless myocardial infarction (MI) leads to increased morbidity and mortality, since patients do not seek medical treatment in a timely manner. We aimed to explore whether reduced systemic pain perception in response to experimental stimuli and pain related personality variables characterizes painless MI patients., Methods: Level of chest pain intensity was assessed by numerical scale, range from 0 (no pain) to 100 (maximal pain). Heat pain threshold, magnitude estimation of supra-threshold phasic and tonic painful stimuli as well as anxiety and pain catastrophizing scores were assessed in 92 acute MI patients; 67 with and 25 without chest pain, respectively. All experimental stimuli were performed by Thermal Sensory Analysis (TSA) and applied to the right forearm., Results: Greater intensity of chest pain scores was inversely correlated with lower pain threshold (r=-0.417, p<0.001), and directly associated with higher pain scores in response to the heat pain (r=0.354, p=0.002). Patients with painful MI demonstrated lower pain threshold (41.9+/-3.6 degrees C vs. 44.9+/-3.8 degrees C, p=0.001) and higher catastrophizing level (10.6+/-12.0 vs. 5.4+/-8.8, p=0.032). Logistic regression analysis revealed that older age and lower pain scores in response to supra-threshold painful stimuli were associated with greater risk for painless MI. The demographic variables, history of ischemic heart, risk factors for coronary artery disease, ST-T segment changes on ECG and troponin levels were similar in both groups., Conclusions: This study suggests that reduced systemic pain perception as well as cognitive personality variables play an important role in the etiology of painless MI.

Objectives: To analyze the long-term results of Boerema anterior gastropexy using the Visick grading system in a university teaching hospital., Methods: Retrospective review of 247 children with severe or complicated gastroesophageal reflux disease (GERD). Patients who underwent primary gastropexy between 1990 and 2001 were divided in 3 groups: (A) neurologic impaired patients (n = 83); (B) esophageal atresia patients (n = 36); and (C) patients without underlying disease (n = 128). The median length of follow-up after gastropexy was 7 years and 8 months (range, 1.5-13 years). Follow-up was carried out using a standardized questionnaire and was obtained by telephone. Postoperative recurrence of symptoms during follow-up was considered as failure of the operation., Results: Postoperative complications occurred in 20 patients (24%) in group A, in 13 patients (36%) in group B and in 23 patients (18%) in group C. Thirty-three patients died during the follow-up period, 5 of whom during the postoperative period. Six children could not be traced; thus, 208 were available for long-term follow-up. Postoperative failures occurred in 12 patients (23%) in group A, in 11 patients (31%) in group B and in 17 patients in group C (14%). Reoperation for recurrence of symptoms due to GERD was performed in 6 patients in group A, in 7 patients in group B and in 2 patients in group C. The final outcome at the time of interview was successful in 81% of group A, in 88% of group B and in 91% of group C., Conclusions: In the long term, Boerema anterior gastropexy is an effective operation for complicated GERD in children without underlying disease as well as in neurologically impaired children and patients with esophageal atresia.

Objective: The objective of this study was to test whether the frequent association between liver enzyme elevations and various components of the metabolic syndrome is associated with higher C-reactive protein (CRP) levels., Methods and Results: Alanine aminotransferase (ALT), alkaline phosphatase (Alk-P), and high-sensitivity CRP were measured in 1740 subjects. Adjusted geometric mean CRP was calculated for subjects with normal and elevated ALT and for subjects with normal and elevated Alk-P, adjusting for age, sex, smoking, physical activity, body mass index, fasting glucose, triglycerides, the presence of hypertension and low HDL cholesterol, and use of aspirin or hormone replacement therapy. Adjusted CRP levels were higher in subjects with elevated ALT (2.21 versus 1.94 mg/L, P=0.028) or elevated Alk-P (2.58 versus 1.66 mg/L, P<0.0001). Logistic regression showed that compared with subjects with normal liver function tests, the adjusted odds for high-risk CRP (>3 mg/L) were significantly higher in subjects with elevated ALT (OR, 1.5; 95% CI, 1.2 to 1.9, P=0.002) or elevated Alk-P (OR, 2.1; 95% CI, 1.7 to 2.6, P<0.0001)., Conclusions: Elevations of liver enzymes are associated with higher CRP concentrations. Hepatic inflammation secondary to liver steatosis is a potential contributor to the low-grade inflammation associated with the metabolic syndrome.

Background: In contrast to adults, little is known about the epidemiology and the best therapeutic regimen for cholelithiasis and sludge in children., Methods: Eighty-two children with cholelithiasis detected by ultrasonography were studied from 0 to 18 years of age with regard to cause, symptomatology, and treatment outcome. Seventy-five children with sludge within the same age group were studied as well., Results: Idiopathic gallstones were found in 19 (23%) patients, and 32 (39%) had gallstones in association with a hemolytic disease. Predominant factors associated with the development of gallstones and clinical presentation differed with age. In patients with sludge, total parenteral nutrition and systemic infection or administration of antibiotics were most frequently found to be possible predisposing factors. Sludge can develop and disappear within a few days. Complications of cholelithiasis were observed in 13 patients. Cholecystectomy was performed in 41 patients and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction in 9 patients; 32 children were not treated. After a follow-up (mean, 4.6 years) in 50 patients, 46% of the children who had cholecystectomy or therapeutic ERCP experienced clinical recurrence of abdominal symptoms. In the patients who did not receive surgical or endoscopic therapy during the follow-up, no complications occurred, and only one patient experienced abdominal symptoms during follow-up., Conclusions: The difference in associated conditions may indicate that the pathogenesis of cholelithiasis and sludge differ as well. Furthermore, sludge should be viewed as a dynamic condition not predisposing for the development of gallstones, per se. Cholecystectomy should not be performed routinely but only after careful selection in patients at risk for complications.

Background: Intussusception is the most common cause of intestinal obstruction in young children, and high mortality rates remain a problem in developing countries. The purpose of this study was to describe and elucidate the differences in outcome between groups of children with intussusception in Indonesia, a developing country, and The Netherlands, a developed country., Methods: In this retrospective review, 176 patients were studied in three types of hospitals. A comparison was made among children treated at a primary care rural hospital in Indonesia, at a secondary care urban hospital in Indonesia, and at a tertiary care urban hospital in The Netherlands., Results: Children in the rural community hospital in Indonesia were more severely ill at arrival and had a significantly longer duration of symptoms, an increased incidence of nonviable bowel, and a mortality rate of 20%, in contrast to a mortality rate of 3% in the urban hospital in Indonesia and no deaths in the Dutch hospital., Conclusions: The mortality of children with intussusception in rural Indonesia is much higher than in urban Indonesia or in The Netherlands, probably because of delayed treatment, which results in more patients undergoing surgery in worse physical condition.

Purpose: Tachypnea in children is associated with respiratory disorders and nonrespiratory disorders such as cardiac disease, metabolic acidosis, fever, pain, and anxiety. Pulmonary embolism is seldom considered by pediatricians as a cause of tachypnea., Patients and Methods: Three children of various ages with persistent tachypnea are described: a girl after orthopedic surgery for kyphoscoliosis, a boy with nephrotic syndrome, and a neonate with Hirschsprung disease. Other causes of tachypnea were diagnosed and treated before pulmonary embolism was considered., Results: Ventilation-perfusion scanning appeared to be highly probable for pulmonary embolism in these patients. Anticoagulant therapy was started., Conclusion: Pulmonary embolism should be kept in mind in children with tachypnea, especially when other risk factors for venous thromboembolism are present, to avoid delay in anticoagulant treatment and a fatal outcome.

In scoliosis, the Cobb measure of curve severity has been recommended over the Ferguson method because it had greater magnitude and appeared more sensitive to changes during progression and after treatment. This study made comparisons between the Cobb and Ferguson measures in radiographs of patients with idiopathic scoliosis to test whether the methods were really different, and to compare their precision. In 138 observations of 77 untreated patients there was a very high correlation (R2 = 0.98) between Cobb and Ferguson angle, with Cobb angle averaging 1.35 times greater. For sequential measures (mean interval 10 months), the percent changes agreed closely (R2 = 0.5). The relationship between Cobb and Ferguson angles remained the same in measurements of 24 patients wearing a brace compared with the unbraced condition and in 18 patients measured before and after Harrington rod surgery. Repeated measurements were made by three observers with the apex and end vertebrae pre-marked and held constant. For Cobb angle, the greatest range of measurements on any film was 8 degrees (pooled SD = 1.3 degrees). For Ferguson angle the greatest range was also 8 degrees (pooled SD = 1.8 degrees). Ferguson angle was slightly more sensitive to incorrect selection of end vertebrae. It was concluded that both methods can be useful for measuring curve magnitude. Ferguson angle should be measured and then adjusted by multiplying it by 1.35 in situations where Cobb angle measurement is technically difficult or invalid. Ferguson angle is better suited to automated measurement.

In 1981, we designed a protocol to treat displaced supracondylar fractures using a modified technique of closed reduction and percutaneous pinning. After the fracture was internally fixed, intraoperative anteroposterior (AP) radiographs of each distal humerus were compared. The reduction and pinning was accepted only if the radiographs demonstrated that Baumann's angle was < or = 4 degrees of that on the normal side. Seventy-one patients had clinical and radiographic evaluations at an average of 2 years 6 months after the operation. According to Flynn's criteria, the results were satisfactory in 70 patients and unsatisfactory in one. No patient had a cubitus varus deformity at follow-up evaluation.

Background: Fibrinolytic therapy is associated with frequent rethrombosis. There is evidence of both increased coagulation and platelet activation., Methods and Results: Platelet-rich plasma (PRP) or washed platelets were incubated with the fibrinolytic agents urokinase, recombinant tissue-type plasminogen activator (rt-PA), or plasmin at concentrations consistent with those in the plasma of patients treated for myocardial infarction. All of the fibrinolytic agents induced a more rapid generation of thrombin and decreased the clotting times of non-contact-activated PRP than in untreated PRP. This effect was not blocked by the inclusion of thrombin inhibitors during the fibrinolytic treatment. Washed platelets derived from rt-PA-treated PRP induced more rapid thrombin generation when resuspended in untreated plasma or treated plasma. Washed platelets were treated with plasmin, rt-PA, and urokinase and added to platelet-poor plasma. Platelets treated with either plasmin or rt-PA increased the ability of washed platelets to support thrombin generation, but urokinase was without significant effect., Conclusions: These results indicate not only that plasmin can cause increased platelet support of prothrombin activation but also that rt-PA in the absence of plasminogen can have a direct effect on the platelet, which increases thrombin generation.

The effectiveness of allograft bone for posterior spinal fusion in neuromuscular scoliosis is controversial. Thirty patients with cerebral palsy, treated with posterior spinal fusion, were divided into two groups. Group 1 consisted of 18 patients treated by posterior spinal fusion using autogenous bone graft. Group 2 consisted of 12 patients treated by posterior spinal fusion using freeze-dried allograft bone. The average preoperative curve of 70 degrees in Group 1 was corrected to 35 degrees (50% correction). At 3.2 years average follow-up, the curves averaged 51 degrees (46% loss of correction). The average preoperative curve of 80 degrees in Group 2 was corrected to 39 degrees (51% correction). At 3.5 years average follow-up, the curves averaged 54 degrees (38% loss of correction). Anesthesia time decreased from 344 to 281 minutes (p less than 0.05), and intraoperative blood loss decreased from 2730 to 1740 ml (p less than 0.025) when allograft bone was used as a substitute for autograft bone. Freeze-dried allograft bone is a readily available, safe, and effective substitute for autogenous bone graft in patients with cerebral palsy undergoing posterior spinal fusion.

In a 2-year-old boy with untreated cystic fibrosis, an acute deterioration of his chronic respiratory insufficiency developed due to bilateral pneumonia. This condition caused acute right-sided heart failure and nontransmural myocardial infarction of the inferior wall. In concordance with this diagnosis, a marked increase of CPK-MB levels combined with transient severe ischemia on the ECG and the absence of myocardial injury at echocardiography was seen. At 3 years follow-up, he was in good clinical condition.

A case is presented in which a delay in diagnosis and treatment of osteomyelitis occurred because of diagnostic confusion between the patient's osteomyelitis and his coincident infantile cortical hyperostosis.

The Boerhaave syndrome is classically considered a panmural perforation of the distal esophagus secondary to forced vomiting or retching. A variant of the syndrome is described in which only the outer longitudinal muscle layer of the esophagus was torn, and in this case most of the usual radiological findings were absent. The clinical, radiological, and surgical findings are discussed.