Development of an Extended Cardiovascular SOFA Score Component Reflecting Cardiac Dysfunction with Improved Survival Prediction in Sepsis: An Exploratory Analysis in the Sepsis and Elevated Troponin (SET) Study.

INTRODUCTION: The cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score does not correspond with contemporary clinical practice in sepsis or identify impaired cardiac function. Our aim was to develop a modified cardiovascular SOFA component that reflects cardiac dysfunction and improves the SOFA score's 30-day mortality discrimination. METHODS: A cohort of sepsis patients from a previous study was divided into a training (n = 250) and test cohort (n = 253). Nine widely available measures of cardiovascular function were screened for association with 30-day mortality using natural cubic spline. High-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) and heart rate (HR) were transformed into ordinal variables (0-4 points). The presence of atrial fibrillation (AF) was assigned two points. The SOFA score was extended by adding the variable points in different weights and combinations. The best-performing cardiac-extended model (CE-SOFA) was evaluated in the test cohort. Improved prognostic discrimination and calibration were assessed using logistic regression, area under receiver operating characteristic curves (AUC), Net Reclassification Improvement (NRI) index, and DeLong and Hoshmer-Lemeshow tests. RESULTS: In the training cohort, all differently weighted and combined models using hs-cTnT, NT-proBNP and AF points added to the SOFA score showed improved discriminative ability (AUC 0.67-0.75) compared to the SOFA score (AUC 0.62; NRI P < .001; DeLong P ≤ .001). In the test cohort, CE-SOFA demonstrated improved 30-day mortality discrimination compared to the SOFA score (AUC 0.72 vs 0.68), exhibiting good calibration and significantly improved discrimination using the NRI index (P = .009) but not the DeLong test (P = .142). CONCLUSIONS: The CE-SOFA model reflects cardiac dysfunction and improves 30-day mortality discrimination in sepsis. External validation is the next step to further substantiate a revised cardiovascular component in a future SOFA 2.0.

Physical activity and fitness.

There is unanimous agreement that regular exercise is essential for optimal function of the human body. It is evident that extrinsic factors, such as diet and exercise habits, are reflected in the morbidity and mortality statistics, especially in aging. Aging is obligatorily associated with reduced maximal aerobic power and reduced muscle strength, ie, with reduced physical fitness. As a consequence of diminished exercise tolerance, a large and increasing number of elderly people will be living below, at, or just above "thresholds" of physical ability, needing only a minor intercurrent illness to render them completely dependent. Physical training can readily produce a profound improvement of functions also essential for physical fitness in old age. From a nutritional viewpoint one advantage of physical activity, and increased metabolic rate, is that a higher energy intake can better secure an adequate intake of essential nutrients.

Free fatty acids and exercise.

Although the great explorers were well aware that eating fat was an efficient way to meet their large energy demand, it was not until some decades into this century that it could be demonstrated that lipids are metabolized directly by contracting skeletal muscles. The 1950s produced the first studies with [14C]-tagged fatty acids (FAs), proving that fat is transported into the cell as FAs. An FA-transporting protein that is present in the sarcolemma and in the cytoplasma has been identified. For FA transport into the mitochondria, carnitine and carnitine transferase are needed. It is still unclear how the use of lipids as an energy source for the muscle during exercise is limited. The supply of free fatty acids (FFAs) far exceeds what is taken up by the muscle. Seldom more than 2-4% of the amount of FFAs delivered to an exercising limb is taken up by the muscles and only part of it is oxidized. Physical training induces changes that enhance the uptake of FAs by the contracting muscles, and a larger fraction of this uptake is oxidized, but it is not yet clear which mechanism is behind this adaptation. What is known is that this uptake occurs despite no elevation in the amount of FA supplied to the limb.

Relative pre- and postjunctional roles of noradrenaline and adenosine 5'-triphosphate as neurotransmitters of the sympathetic nerves of guinea-pig and mouse vas deferens.

Experiments were designed to examine the relative roles of noradrenaline and adenosine 5'-triphosphate (ATP) as mediators of the contractile responses of the guinea-pig and the mouse vas deferens to electrical nerve stimulation. To study possible prejunctional actions of the agents used, in some experiments their effects on the secretion of [3H]noradrenaline were determined. The contractile responses were recorded with force displacement transducers. Pharmacological techniques were employed to examine the pre- and/or postjunctional effects mediated by noradrenaline and ATP, respectively. Noradrenaline-mediated components were "removed" by depleting the neuronal stores of noradrenaline (by pretreatment with reserpine), or by addition of adrenoceptor-blocking agents. ATP-mediated components were "removed" by desensitizing ATP receptors (with the stable analogue alpha, beta-methylene ATP). The results permit three major conclusions: (1) In both species noradrenaline and ATP "auto-inhibit" mechanisms responsible for transmitter secretion; the prejunctional effects of ATP are less marked in the mouse vas deferens, and in both species much weaker than those mediated by noradrenaline, acting via alpha 2-adrenoceptors. (2) In these species, both noradrenaline and ATP participate in the generation of both phases of the contractile responses to nerve stimulation. The relative roles of each vary with the frequency and train length of stimulation, and also with the species. The main transmitter of "phase I" contractions in guinea-pig vas deferens is ATP, and in the mouse vas deferens, noradrenaline. "Phase II" contractions are triggered mainly by noradrenaline, in both species. Sympathetic neuroeffector transmission in these tissues can be accounted for almost entirely in terms of dynamic interplay between pre- and postjunctional actions of noradrenaline and ATP. (3) The results are compatible with the hypothesis that ATP is a co-transmitter with noradrenaline in these sympathetic nerves.

Discrete events measure single quanta of adenosine 5'-triphosphate secreted from sympathetic nerves of guinea-pig and mouse vas deferens.

Intracellularly recorded excitatory junction potentials in smooth muscle cells, and the first time differentials of their rising phases ("discrete events") were used to analyse transmitter secretion from the postganglionic sympathetic nerves of guinea-pig and mouse vas deferens. The aim was to determine whether the transmitter causing these responses is noradrenaline or adenosine 5'-triphosphate (ATP). Depletion of the noradrenaline stores following treatment with reserpine reduced the frequency of occurrence, but not the amplitude, of spontaneous junction potentials and discrete events. Nerve stimulation could still evoke "fast" junction potentials and discrete events, normal in appearance, but "slow" junction potentials were reduced in amplitude and had shorter times to peak. In contrast, desensitization of ATP receptors by alpha, beta-methylene ATP abolished spontaneous and stimulus-induced "fast" (but not "slow") junction potentials and discrete events, reversibly. It is concluded that it is not noradrenaline, but ATP or some related compound which causes spontaneous and "fast" stimulus-induced junction potentials, and discrete events. The present and earlier data show that discrete events reflect the secretion of individual quanta of ATP (or quanta of "ATP + noradrenaline", if both are secreted in parallel from the same vesicle) from postganglionic sympathetic nerve terminals in guinea-pig and mouse vas deferens.

Neuropeptide Y--a cotransmitter with noradrenaline and adenosine 5'-triphosphate in the sympathetic nerves of the mouse vas deferens? A biochemical, physiological and electropharmacological study.

UNLABELLED: A combination of biochemical, physiological and electropharmacological methods was employed to examine the occurrence of neuropeptide Y and the pre- and postjunctional effects of this peptide on sympathetic neuromuscular transmission in the mouse vas deferens. This tissue had a high content of neuropeptide Y-like immunoreactive material, suggesting a dense innervation by neuropeptide Y-containing nerve fibres. Addition of neuropeptide Y at concentrations from 5 X 10(-9) to 5 X 10(-7) M induced both pre- and postjunctional effects in vitro. Neuropeptide Y per se induced a rise in the resting tension, and "instantly" potentiated the contractile effects of exogenous noradrenaline and of the stable adenosine 5'-triphosphate (ATP) analogue, alpha,beta-methylene ATP. Neuropeptide Y reduced the secretion of [3H]noradrenaline evoked by electrical nerve stimulation, and selectively depressed the stimulus-evoked, but not the spontaneously occurring excitatory junction potentials in smooth muscle cells. Further, neuropeptide Y reduced the amplitudes of the twitch contractions evoked by electrical field stimulation with short stimulus trains at 10 Hz, and also (although to a smaller extent) the delayed contractile response to longer trains of nerve stimuli. The pre- and postjunctional effects of neuropeptide Y were not changed by alpha- or beta-adrenoceptor blocking agents, or by tachyphylaxis to the effects of ATP, or by the calcium channel blocker nifedipine. IN CONCLUSION: sympathetic neuromuscular transmission in the mouse vas deferens may be mediated not only by noradrenaline and ATP, but also by neuropeptide Y.(ABSTRACT TRUNCATED AT 250 WORDS)

Presynaptic receptors and modulation of noradrenaline and ATP secretion from sympathetic nerve varicosities.

Our results in the model tissues examined show (1) that alpha 2 agonist(s) depressed the secretion of NA and ATP caused by nerve stimulation at low frequency, (2) that the secretion of both NA and ATP was moderately autoinhibited, under conditions when endogenous NA was shown to accumulate extracellularly, (3) that a K+ channel blocking agent increased much more strongly than alpha 2-adrenoceptors block the secretion of both NA and ATP, and also amplified enormously the NA-mediated neurogenic contraction, (4) that, therefore, a high K+ efflux is likely to be much more important than alpha 2-adrenoceptor-mediated autoinhibition for maintaining a low release probability in sympathetic nerve varicosities, and (5) that the alpha 2-adrenoceptor agonist, clonidine, or the Ca2+ channel blocking agent, Cd2+, inhibited transmitter secretion, at least in part, via targets "upstream" of the varicosity.

A 33-yr follow-up of peak oxygen uptake and related variables of former physical education students.

In 1949, 27 female and 26 male physical education students were studied at a mean age of 22 and 25 yr, respectively. They were restudied in 1970 and 1982. Measurements included oxygen uptake, heart rate, and pulmonary ventilation during submaximal and maximal exercise on a cycle ergometer and treadmill. After 21 yr, peak aerobic power was significantly reduced, from 2.90 to 2.18 l/min and from 4.09 to 3.28 l/min for women and men, respectively. After another 12 yr, the 1970 maxima were not reduced further. From 1949 to 1982 there was a decrease in peak heart rate from 196 to 177 beats/min in women and from 190 to 175 beats/min in men (P < 0.05). Highest pulmonary ventilation did not change significantly. At an oxygen uptake of 1.5 l/min, the heart rate was the same in 1949 as in 1982. In conclusion, the physical fitness level of the subjects was well above average for these ages. From 1970 to 1982 there was no decline in the average peak aerobic power, a finding possibly related to increased habitual physical activity.

Disposal of lactate during and after strenuous exercise in humans.

Heavy dynamic exercise using both arm and leg muscles was performed to exhaustion by seven well-trained subjects. The aerobic and anaerobic energy utilization was determined and/or calculated. O2 uptake during exercise and during 1 h of recovery was measured as well as splanchnic and muscle metabolite exchange. Glycogen and lactate content in the quadriceps femoris was determined before exercise, immediately after exercise, and after a recovery period. In four male subjects the estimated mean lactate production during exercise was 830 mmol. The splanchnic uptake of lactate during recovery was 80 mmol, and the calculated maximum amount oxidized during the recovery period was 330 mmol. About 60 mmol were accounted for in the body water at the end of the rest period. The remaining 360 mmol of lactate were apparently resynthesized into glycogen in muscle via gluconeogenesis. It is concluded that approximately 50% of the lactate formed during heavy exercise is transformed to glycogen via glyconeogenesis in muscle during recovery and that lactate uptake by the liver is only 10%.

J.B. Wolffe Memorial Lecture. "Why exercise?".

There is a pronounced plasticity and adaptability in the structural and/or functional properties of cells, tissues, and organ systems in the human body when exposed to various stimuli. While there is unanimous agreement that regular exercise is essential for optimal function of the human body, it is evident that extrinsic factors, such as diet and exercise habits, are reflected in the morbidity and mortality statistics, especially in the aged. Aging is obligatorily associated with reduced maximal aerobic power and reduced muscle strength, i.e., with reduced physical fitness. As a consequence of diminished exercise tolerance, a large and increasing number of elderly persons will be living below, at, or just above "thresholds" of physical ability, needing only a minor intercurrent illness to render them completely dependent. Physical training can readily produce a profound improvement of functions essential for physical fitness in old age. Adaptability to regular physical activity serves to cause less disruption of the cell's "milieu interieur" and minimizes fatigue, thereby enhancing performance and the economy of energy output during exercise.

Physiological characteristics of classical ballet.

The aerobic and anaerobic energy yield during professional training sessions ("classes") of classical ballet as well as during rehearsed and performed ballets has been studied by means of oxygen uptake, heart rate, and blood lactate concentration determinations on professional ballet dancers from the Royal Swedish Ballet in Stockholm. The measured oxygen uptake during six different normal classes at the theatre averaged about 35-45% of the maximal oxygen uptake, and the blood lactate concentration averaged 3 mM (N = 6). During 10 different solo parts of choreographed dance (median length = 1.8 min) representative for moderately to very strenuous dance, an average oxygen uptake (measured during the last minute) of 80% of maximum and blood lactate concentration of 10 mM was measured (N = 10). In addition, heart rate registrations from soloists in different ballets during performance and final rehearsals frequently indicated a high oxygen uptake relative to maximum and an average blood lactate concentration of 11 mM (N = 5). Maximal oxygen uptake, determined in 1971 (N = 11) and 1983 (N = 13) in two different groups of dancers, amounted to on the average 51 and 56 ml X min-1 X kg-1 for the females and males, respectively. In conclusion, classical ballet is a predominantly intermittent type of exercise. In choreographed dance each exercise period usually lasts only a few minutes, but can be very demanding energetically, while during the dancers' basic training sessions, the energy yield is low.

Maximal oxygen uptake "classical" versus "contemporary" viewpoints.

In two articles Timothy Noakes proposes a new physiological model in which skeletal muscle recruitment is regulated by a central "govenor," specifically to prevent the development of a progressive myocardial ischemia that would precede the development of skeletal muscle anaerobiosis during maximal exercise. In this rebuttal to the Noakes' papers, we argue that Noakes has ignored data supporting the existing hypothesis that under normal conditions cardiac output is limiting maximal aerobic power during dynamic exercise engaging large muscle groups.

Nonsubmerged implants in the treatment of the edentulous upper jaw: a prospective clinical and radiographic study of ITI implants--results after 1 year.

BACKGROUND: A new generation of ITI implants, including a hollow cylinder, a hollow screw, and a solid screw, was described in 1988. Currently, the solid screw is the main alternative. PURPOSE: The aim of this study was to gain further clinical documentation of ITI solid-screw implants used in the edentulous upper jaw. This is a report 1 year after loading. MATERIALS AND METHODS: Twenty-eight patients with edentulous upper jaws (mean age, 57 yr) were supplied with four to eight ITI solid-screw implants in the upper jaw. In total, 167 implants (3.3 and 4.1 mm in diameter) were inserted. The implants were loaded about 7 months postoperatively. All patients were supplied with fixed screw-retained bridges. RESULTS: Twelve implants failed: 10 prior to loading and 2 after. Overall implant survival rate was 92.8%. Three of the five patients with implant loss were smokers. Signs of peri-implantitis were found in seven patients, affecting 12 implants. Mean marginal bone level at the loading of the implants (7 months after insertion) was situated 4.7 mm from the reference point of the implant. There was no significant change between loading and the 1-year examination. However, at several implants, the bone level at baseline was situated far apical of the reference point, indicating a bone loss before loading. CONCLUSIONS: The ITI screw implants, used in the edentulous upper jaw, had a survival rate of 92.8%. Mean bone loss between loading and the 1-year examination was 0.1 mm. Some implants had a bone level indicating a significant bone loss before loading. Peri-implantitis was found at about 7.2% of the implants inserted and at 25% of the failing implants.

Nonsubmerged implants in the treatment of the edentulous lower jaw: a 5-year prospective longitudinal study of ITI hollow screws.

BACKGROUND: Although most implant systems have been designed for a two-stage surgical technique, a one-stage surgical technique has always been advocated for the ITI Dental Implant System (Straumann AG, Waldenburg, Switzerland). A new generation of ITI implants was presented in 1988 and included a hollow cylinder, a hollow screw, and a solid screw. PURPOSE: The goal of this study was to evaluate the one-stage surgical technique in connection with the ITI hollow screw in a longitudinal study over 5 years. MATERIALS AND METHODS: Forty-six patients with edentulous lower jaws were supplied with ITI hollow-screw implants. Patients who requested an overdenture (n = 18) had four implants inserted; those who requested a fixed bridge (n = 28) had five to six implants. The patients have been followed annually for 5 years. There was a dropout of three patients (6.5%); one patient did not want to cooperate, one moved from the area, and one was deceased. The clinical examinations included bridge removal for evaluation of the individual implant stability in connection with the 1-, 3-, and 5-year examinations. Radiographic examinations were performed with intraoral radiographs and the long-cone technique. RESULTS: The survival rate after 5 years was 95.7%. The success rate (in which implants undergoing treatment of peri-implantitis were not counted as successes) was 91.4%. The mean marginal bone loss between the baseline and the 1-year examination was 0.1 mm and between the 1- and 5-year examinations was 0.1 mm. These changes in marginal bone level were not significant. CONCLUSIONS: The success rate of ITI hollow-screw implants in the edentulous mandible was 91.4% after a 5-year observation period. There was no significant change in mean bone level between the loading of the implants and the 5-year examination. Peri-implantitis was diagnosed in three patients with poor oral hygiene, and it affected six implants. Five of these failed in spite of treatment.

Astra Tech and Brånemark System implants: a prospective 5-year comparative study. Results after one year.

BACKGROUND: Endosseous dental implants are used frequently, and many implant systems are available. The scientific documentation of the implant system presents a great variation, and it is often difficult to compare studies of different systems. PURPOSE: The aim of this study was to compare two Swedish implant systems (Astra Tech and Brånemark System implants), in a prospective randomized study. MATERIALS AND METHODS: Sixty-six patients were equally distributed between the two implant systems; 184 Astra Tech and 187 Brånemark System implants were used. The patients have been followed annually with clinical and radiographic examinations. The results after 1 year are reported. RESULTS: The abutment procedure was found to be easier and less time-consuming with Astra Tech than with Brånemark implants. The operation times in minutes (mean +/- SEM) were for the respective implant 35 +/- 4.0 and 51 +/- 4.8 in the maxilla and 32 +/- 3.8 and 43 +/- 2.4 in the mandible. The differences in both cases were significant: p < .02 and p < .05, respectively. The failure rate for Astra Tech implants was 0.5% and for Brånemark implants 4.3%. The difference was significant (p < .05); however, taking into account that five of the eight implant losses in the Brånemark implant group occurred in one patient, an intraindividual correlation cannot be excluded. Therefore, this result should be interpreted with caution. The marginal bone level changes were examined already from the fixture installation. The major bone loss was found between fixture installation and baseline. This bone loss was several times greater than the bone loss between the baseline and the 1-year follow-up. The total bone loss during the observation period did not differ significantly between the systems, but they had different resorption patterns. The bone loss in the upper jaw between baseline and 1-year follow-up was 0.22 +/- 0.14 and 0.03 +/- 0.09 mm for the Astra Tech and Brånemark implants, respectively. In the lower jaw, the loss was -0.31 for both systems. The frequency of plaque accumulation and bleeding on probing did not differ between the implant systems. CONCLUSIONS: Abutment connection with Astra Tech implants was simpler than the corresponding surgery with Brånemark System implants and the survival rate of Astra Tech implants was higher than that of Brånemark system implants.

Combination of natural teeth and osseointegrated implants as prosthesis abutments: a 2-year longitudinal study.

Twenty-three patients with Kennedy Class I mandibular dentition were supplied with prostheses in the posterior parts of the mandible. On one side they were given a prosthesis supported by two implants (prosthesis Type I) and on the other side they received a prosthesis supported by one implant and one natural tooth (prosthesis Type II). Sixty-nine fixtures were inserted and 46 prostheses constructed. Eight of the fixtures were lost during the observation period. The failure rate of the implants was about the same in the two types of prostheses; five fixtures belonged to prostheses Type I (10.9%) and two fixtures belonged to prostheses Type II (8.7%), while one fixture was lost prior to loading. From a theoretical point of view, the combination of a tooth and an osseointegrated implant should encounter problems with regard to the difference in bone anchorage and there should be a risk of biomechanical complications. However, the results of this study did not indicate any disadvantages in connecting teeth and implants in the same restoration.

Osseointegrated implants in edentulous jaws: a 2-year longitudinal study.

Osseointegrated implants in 50 edentulous jaws were studied during a 2-year observation period. The implant survival rate was 89% in the maxillae and 97% in the mandibles. The marginal bone loss averaged 1.7 mm in the maxillae and 1.1 mm in the mandibles. Most of this bone loss occurred during the first year. The bone loss was greater in jaws with a preoperatively minor resorption of the alveolar ridge than in those with moderate or advanced resorption. The bone loss was also greater at the medially positioned implants than at those more posterior.

Applicability of osseointegrated oral implants in the rehabilitation of partial edentulism: a prospective multicenter study on 558 fixtures.

Nine clinical centers using the Brånemark System participated in a prospective study of 159 partially edentulous patients between 18 and 70 years of age. Clinical parameters evaluated were plaque index, gingivitis, pocket depth, bleeding index, tooth mobility, and stomatognathic function. Initially, 558 fixtures were placed and 521 remained in the study following prosthesis placement (199 prostheses in 154 patients). Fixtures were lost or unaccounted for because of nonintegration prior to prosthesis fabrication (19), patient withdrawal (11), prosthodontic reasons (6), and failure during prosthetic procedures (1). Failure was primarily attributable to unfavorable bone quality, sex (more in males), and smaller fixture size. Complications and failure related to other patient characteristics are presented. After 1 year of a 5-year study, preliminary results suggest that a success rate equal to or better than that obtained with edentulous patients may be expected.

Planning and control of vertical dimension in Le Fort I osteotomies.

Depending on the different anatomy of the soft and hard tissues, concavity or convexity of the face, measurements of inferior or superior repositioning of the maxilla may be less predictable when using only the osteotomy site for this calculation. A more reliable method would be to measure the distance from a bone mark in the forehead to the incisor edges. This method has been practiced by our clinic during the past five years. The method is thought to offer a more accurate estimation of the position of the upper anterior teeth in relation to the lip, although one must anticipate a certain degree of postoperative relapse especially concerning inferior repositioning. In order to evaluate the accuracy of our method, a comparison has been made of the calculated vertical repositioning and the surgical results in two groups. In group I (12 individuals) conventional estimation of maxillary repositioning in the osteotomy line was made; in group II (12 individuals) measurements were made from a bone mark on the forehead to the incisor edges. A satisfying correlation was found between calculated and achieved results in both groups. In comparison between calculated and immediate postoperative measurements the results showed no statistically significant difference between the two methods.

Extraoral or intraoral approach in the oblique sliding osteotomy of the mandibular rami? Clinical experience and results.

The clinical results of oblique sliding (subcondylar) osteotomy of the mandibular rami performed by the extraoral or intraoral approach were compared. The patient material comprised 40 patients with mandibular prognathism. Twenty patients were operated upon using the extraoral approach and 20 patients were operated on using the intraoral approach. All patients had intermaxillary fixation for 7 weeks. The patients in both groups were followed up for 18 months. The experience of the operations was that the intraoral approach gave a shorter operation time than the extraoral approach. The extraoral approach, however, gave better visibility in the operation field and greater possibilities of manipulating the proximal fragment into an optimal position. In the follow-up evaluation, there were no significant differences between the two surgical techniques with regard to dental relapse, post-operative occlusion and mandibular function.