Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations.

BACKGROUND: COPD exacerbations have negative impact on patients' survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival. METHODS: This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation. RESULTS: Included were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13-41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p <  0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6-3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08-3.1, p <  0.05). CONCLUSIONS: Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.

Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study.

OBJECTIVES: The aim was to compare the burden of environmental shedding of toxigenic Clostridioides difficile among asymptomatic carriers, C. difficile-infected (CDI) patients and non-carriers in an inpatient non-epidemic setting. METHODS: C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive two-step enzyme immunoassay/polymerase chain reaction (EIA/PCR) test in patients with more than three unformed stools/24 hr. C. difficile environmental contamination was assessed by obtaining specimens from ten sites in the patients' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. RESULTS: One hundred and seventeen rooms were screened: 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which three (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of non-carriers odd ratio 12.23 and 11.16 (95% confidence interval 1.5-99.96 p 0.0195, and 1.19-104.49 p 0.035), respectively. DISCUSSION: Here we show that the rooms of C. difficile carriers are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

Reducing drug prescription errors and adverse drug events by application of a probabilistic, machine-learning based clinical decision support system in an inpatient setting.

BACKGROUND: Drug prescription errors are made, worldwide, on a daily basis, resulting in a high burden of morbidity and mortality. Existing rule-based systems for prevention of such errors are unsuccessful and associated with substantial burden of false alerts. OBJECTIVE: In this prospective study, we evaluated the accuracy, validity, and clinical usefulness of medication error alerts generated by a novel system using outlier detection screening algorithms, used on top of a legacy standard system, in a real-life inpatient setting. MATERIALS AND METHODS: We integrated a novel outlier system into an existing electronic medical record system, in a single medical ward in a tertiary medical center. The system monitored all drug prescriptions written during 16 months. The department's staff assessed all alerts for accuracy, clinical validity, and usefulness. We recorded all physician's real-time responses to alerts generated. RESULTS: The alert burden generated by the system was low, with alerts generated for 0.4% of all medication orders. Sixty percent of the alerts were flagged after the medication was already dispensed following changes in patients' status which necessitated medication changes (eg, changes in vital signs). Eighty-five percent of the alerts were confirmed clinically valid, and 80% were considered clinically useful. Forty-three percent of the alerts caused changes in subsequent medical orders. CONCLUSION: A clinical decision support system that used a probabilistic, machine-learning approach based on statistically derived outliers to detect medication errors generated clinically useful alerts. The system had high accuracy, low alert burden and low false-positive rate, and led to changes in subsequent orders.

Low ALT blood levels predict long-term all-cause mortality among adults. A historical prospective cohort study.

BACKGROUND: Increased blood levels of alanine amino transferase (ALT, also known as SGPT; serum glutamic pyruvic transaminase) serve as a marker of liver injury by various mechanisms. Less is known about the clinical implications associated with low-normal ALT levels. Previous studies showed low ALT levels to be associated with poor long-term outcomes among elderlies, serving as a biomarker for increased incidence of frailty and subsequent risk of mortality. However, it has not been determined yet whether low-normal ALT values might be predictive of frailty and mortality in younger, middle-aged adults. METHODS: We conducted a historical prospective cohort analysis. RESULTS: A total of 23,506 adults with ALT levels within the normal range, at the mean age of 48 ± 11 years, participating in an annual screening program for preventive medicine, were followed-up for a median period of 8.5 years during which 638 died. Low-normal ALT values (serum ALT activity <17IU/L) were found to be predictive for increased risk of all-cause mortality (HR=1.6; 95% CI 1.34-1.92; p<0.001). Statistically significant correlation was demonstrated even after applying a multifactorial model correction for age, gender, eGFR, low albumin, arterial hypertension, diabetes mellitus and ischemic heart disease. CONCLUSIONS: We suggest that low-normal ALT values may serve as an independent predictive marker for increased long-term mortality in middle-aged adults.

Long-term results of atrial correction for transposition of the great arteries. Comparison of Mustard and Senning operations.

Few data exists on the differences in long-term outcome between Mustard and Senning operations. We reviewed available data of all hospital survivors of these operations and assessed risk factors for late death and sinus node dysfunction. Of those patients undergoing the Mustard operation, 60 were hospital survivors (46 simple transposition, 14 complex); of those patients undergoing the Senning operation, 62 were hospital survivors (43 simple, 19 complex). Median duration of follow-up was 16 years (maximum 25 years) for Mustard operation, 11 years (maximum 20 years) for Senning operation. No reoperations were done, except for pacemaker implantation. No differences were found between the two groups with regard to baffle-associated problems, right ventricular failure, sudden death (6% in both groups), and functional status at final follow-up (New York Heart Association class I or II, except for four patients). For patients undergoing the Mustard operation, survival at 16-year follow-up was 91% with simple transposition and 60% with complex transposition (p = 0.027); for both groups of patients undergoing the Senning operation, survival at 16-year follow-up was 78%. Survival in the absence of rhythm disturbance at 16-year follow-up was 18% for Mustard operation and 53% for Senning operation (p < 0.001). In multivariate analysis, significant independent risk factors for late death turned out to be complex transposition (versus simple) and active arrhythmias. The only significant risk factor for the occurrence of sinus node dysfunction was the Mustard operation. We conclude that apart from the difference in the loss of sinus rhythm, no differences were found in the long-term clinical results of the two types of operations.

The arterial switch operation. An eight-year experience.

Sixty-six patients (23 neonates with transposition of the great arteries and intact ventricular septum, 33 infants and children with transposition and a large ventricular septal defect, and 10 with double-outlet right ventricle with a subpulmonary ventricular septal defect have received an arterial switch repair since 1977. Eight (one with transposition and intact ventricular septum, six with transposition and ventricular septal defect, and one with double-outlet right ventricle with subpulmonary ventricular septal defect) died in the hospital. All other patients have had follow-up as of June, 1985. Including the hospital deaths, the 11 month actuarial survival rate for the entire group was 81%, and no deaths have occurred among the 33 patients alive at that time and traced as long as 8 years. The hazard function for death has only a single early phase, and its 70% confidence limits overlap the hazard function of a matched general population by 12 months after the operation. Incremental risk factors for death included low birth weight (but not weight or age at operation), transposition of the great arteries with large ventricular septal defect, double-outlet right ventricle with subpulmonary ventricular septal defect, and presence of a patent ductus arteriosus. Coronary artery morphology and position of the great arteries were not risk factors. Long aortic cross-clamp time was possibly (p = 0.11) a risk factor. Early date of operation was a risk factor (p = 0.004); thus, predicted 1 year survival rate, including hospital deaths, after the arterial switch operation in 1985 is 99.9% (70% confidence limits 99.0%-100%) for neonates with transposition and intact ventricular septum and 99.7% (98.4%-99.9%) for those with transposition and a large ventricular septal defect or double-outlet right ventricle. The late functional status was excellent, and the rhythm was sinus in 96% of the 55 surviving patients. A formal comparison with the results of the atrial switch repair indicates that the arterial switch repair is superior.

Developmental considerations of mitral valve anomalies.

Atrioventricular valve development is described as following the general principle of junctional invagination and myocardial undermining. We have added considerations of the topographic relations of the developing mitral valve to these principles. Two groups of malformations are then distinguished: the first comprises disturbances of the general principle, the second is related to topographic abnormalities. It is shown that the atrioventricular septal defect, the straddling mitral valve and the isolated mitral cleft all have their own specific developmental backgrounds.

Tricuspid atresia. Morphology of the outlet chamber with special emphasis on surgical implications.

An anatomic study of 28 heart specimens with tricuspid atresia showed 15 hearts with ventriculoarterial concordance and a right-sided anterior outlet chamber. Of these 15 hearts, 12 showed evidence of restricted pulmonary blood flow. In eight of these 12 specimens, an anterior deviation of the outlet septum, relative to the primary septum, was present. This deviation caused a narrowing inside the outlet chamber and functioned as infundibular pulmonary stenosis. The outlet chambers of the 15 hearts with ventriculoarterial concordance were compared with those of 13 hearts with tricuspid atresia and ventriculoarterial discordance and also a right-sided anterior outlet chamber. In the latter group of 13 hearts, five showed evidence of restricted pulmonary blood flow, at least partially caused by posterior deviation of the outlet septum relative to the primary septum. A clear difference in outlet chamber morphology was found without exception between specimens with and without ventriculoarterial concordance. Clinical data in three long-term survivors of the Fontan procedure demonstrate that the special morphology of the outlet chamber can pose surgical problems. Especially in patients with ventriculoarterial concordance, when the outlet chamber is incorporated into the pulmonary circuit, the surgeon must give special attention to the specific morphology to prevent undesirable sequelae.

Growth of an aorta-coronary anastomosis. An experimental study in pigs.

The influence of growth of an aorta-coronary anastomosis, comparable to the coronary translocation anastomosis during the arterial switch operation, was studied in pigs. The anastomosis between the right coronary artery and the aorta did not grow, and this lack of growth may result in stenosis. With another technique, by which the coronary artery was excised with a cuff of aortic wall, the effects caused by absence of growth were circumvented and a normal-sized coronary ostium was present after growth. However, when no cuff was used, stenosis occurred at the suture line and caused growth retardation of the animal as well as histologic damage to the right ventricle.

Nine years' experience of physiological correction of tricuspid atresia: long-term results and current surgical approach.

Fontan's correction has been performed without early death in 24 consecutive patients with tricuspid atresia. Eighteen patients had ventriculoarterial concordance (group I) and six discordance (group II). Late death related to infections occurred in three patients. The follow-up time in group I (16 survivors) ranges from 1 year 10 months to 7 years 5 months (mean 3 years 8 months) and in group II (five survivors) from 2 years 1 month to 5 years 6 months (mean 3 years 6 months). Early postoperative cardiac catheterisation showed arterial pulsatile pressure recordings in the pulmonary artery only in two patients in group I, in whom a valved conduit was used to connect the right atrial appendage with the outlet chamber. Patients with a valved conduit connected with either the pulmonary artery (group II) or the outlet chamber (two patients of group I) showed better preservation of right atrial contractions angiocardiographically and scored better in exercise tests than did patients with a non-valved conduit (14 patients of group I). In the latter patients evidence of regurgitant bloodflow from the outlet chamber into the right atrium was found. Reoperation was necessary in two patients. The outlet chambers showed a substantial increase in diameter after operation. No disturbances of kidney or liver function were found up to seven years after operation. The clinical condition has improved considerably in all survivors. It is concluded that the use of a valved conduit is preferable for connecting the pulmonary artery directly in cases of tricuspid atresia with ventriculoarterial discordance or the outlet chamber when there is ventriculoarterial concordance.

Horizontal submammary skin incision for median sternotomy.

Usual techniques in open-heart operations leave a vertical median skin scar. Especially for women this is rather embarassing since it looks ugly. The use of horizontal submammary skin incision for access to the heart is described here. Although obtaining the usual midsternal exposure takes some extra time, long-term results have shown the value of this approach and its benefit to the patient. The surgical technique is simple, and wound healing, in the long run, is unimpaired.

Differential atrial filling after Mustard and Senning repairs. Detection by transcutaneous Doppler ultrasound.

The dominance of Mustard's operation for transposition of the great arteries has been challenged by the recent revival of Senning's repair because it promises better long-term results in terms of venous obstruction and atrial haemodynamics. These hypotheses were tested by recording jugular venous flow waveforms transcutaneously in 24 postoperative patients with simple complete transposition using a bidirectional Doppler blood velocimeter. Eight patients had undergone Mustard's operation and 16 the Senning alternative; all had previously had a postoperative cardiac catheterisation. Both groups of patients had similar left ventricular, pulmonary arterial, and systemic venous atrial pressures. No child showed any evidence at catheterisation of either mitral regurgitation or of superior vena caval pathway obstruction. These two findings were endorsed by the transcutaneous Doppler recordings. Jugular venous flow in normal children exhibits two maxima, one of atrial filling during ventricular systole, the other of ventricular filling occurs once the tricuspid valve has opened. Both operative procedures diminished the size of the former phase, but the Mustard did so more. After Mustard's operation forward flow during the atrial filling phase was absent in approximately half the cardiac cycles recorded, and severely diminished in the rest. By contrast, there was approximately a 90 per cent appearance of atrial filling waves after Senning's operation which also provided significantly better atrial function than Mustard's procedure in terms of peak velocity of blood entering the atrium and total atrial filling. It is therefore concluded that both procedures compromise atrial volume and compliance but Senning's repair to a much lesser extent.

Anatomical correction of transposition of great arteries with persistent ductus arteriosus. One year after operation.

The postoperative data are described of a boy who had a 'switch' operation for transposition of the great arteries with persistent ductus arteriosus more than a year before. The child is living a normal active life. Electrocardiography, echocardiography, and angiocardiography show persistent abnormality of structure and function of the right ventricle but no evidence of reduced coronary blood flow, coarctation at the suture lines of the great arteries, or aortic regurgitation. Reference is made to an identical case operated upon 2 1/2 years ago.