Digitalisierung und künstliche Intelligenz in Orthopädie und Unfallchirurgie

In the course of digitalization it is becoming increasingly rare for medical documents to be handwritten. As a result, digitalization has already become an integral part of routine patient care but in contrast to other specialist disciplines, such as radiology or laboratory medicine, orthopedics and trauma surgery are still at the beginning of new technologies. Artificial intelligence is not only used in the form of surgical robots in joint surgery or in the design of individualized implants but also provides valuable decision-making aids through appropriate algorithms for diagnosis and treatment. It can be assumed that these technologies will be further developed and used increasingly more in the coming years. Typical examples are intuitively operable and autonomously working programs and systems that support the networking and work of medical personnel and make processes inside and outside inpatient care more precise and less vulnerable to disturbances.     

The early phase of glucose-stimulated insulin secretion requires nitric oxide

Summary Nitric oxide (nitrogen monoxide, NO) acts as a signal transducer in a variety of cells. In the present study rat pancreatic islets were perifused with physiologically relevant glucose concentrations in the presence or absence of various NO-modulating agents. Perifusion in the presence of 0.1–1 mmol/l of the NO synthase inhibitor, N^G-monomethyl-L-arginine or of 10 μmol/l of the NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), resulted in an inhibition of the early phase of glucose-stimulated insulin secretion by 60–65 % and 46 %, respectively. Light- and electron-microscopic studies revealed that pancreatic islets constitutively express NO-synthase in alpha and delta cells, where it is confined to the secretory granules. Therefore, these data indicate that NO may be important in the signal transduction pathway of the early phase of glucose-stimulated insulin secretion. [Diabetologia (1998) 41: 292–299] Received: 3 March 1997 and in revised form: 21 November 1997     

Prognostic value of different laboratory measures of renal function for long-term mortality after contrast media-associated renal impairment

Background: Contrast media‐induced nephropathy (CIN) is associated with markedly increased morbidity and mortality. Although creatinine is at present routinely used to characterize renal function, many studies and guidelines recommend using the estimated glomerular filtration rate (eGFR) since it was found to be much more accurate. Hypothesis: To assess whether the eGFR or creatinine alone provided a better predictive value for long‐term mortality after contrast media‐associated renal impairment. Methods: From a prospective trial with 412 patients undergoing heart catheterization, creatinine and eGFR before and after 24 h, 48–72 h, and 30 d after contrast‐media exposure were assessed as well as long‐term mortality. Results: Univariate Cox regression models identified increases in creatinine after 48 h (hazard rate ratio [HRR] 1.754, 95% confidence interval [CI] 1.134–2.712) and 30 d (HRR 3.157, 95% CI 1.968–5.064) as well as decreases in eGFR after 30 d (HRR 0.962, 95% CI 0.939–0.986) to be significant predictors of long‐term mortality. However, by multivariable Cox regression, only increases in creatinine after 48 h (HRR 1.608, 95% CI 1.002–2.581) and after 30 d (HRR 2.685, 95% CI 1.598–4.511) turned out to be significant and independent predictors of mortality. With regard to a possibly critical threshold of creatinine increase, our data confirmed the historically grown increase in creatinine of 0.5 mg/dl or more during the first 48 h as being associated with increased mortality (p = 0.016, log rank test). Conclusions: Serum creatinine, but not eGFR, was predictive for long‐term mortality, with a threshold of 0.5 mg/dl or more indicating worse prognosis. Copyright © 2010 Wiley Periodicals, Inc. Supported by an unrestricted research grant from Schering AG, Berlin, Germany.     

Free Fatty Acids Link Metabolism and Regulation of the Insulin-Sensitizing Fibroblast Growth Factor-21

OBJECTIVE

Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator–activator receptor (PPAR) α–dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPARα, might modify FGF-21 levels.

RESEARCH DESIGN AND METHODS

The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPARγ activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks.

RESULTS

Oleate and linoleate increased FGF-21 expression and secretion in a PPARα-dependent fashion, as demonstrated by small-interfering RNA–induced PPARα knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect.

CONCLUSIONS

The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity.Fibroblast growth factor (FGF)-21 is a recently discovered metabolic regulator of fasting metabolism. FGF-21 activates glucose uptake in adipocytes, protects animals from diet-induced obesity when overexpressed in transgenic mice, and lowers blood glucose and triglyceride levels when administered to diabetic rodents (1–3). Comparably, glucose- and triglyceride-lowering effects were found in diabetic rhesus monkeys during chronic FGF-21 treatment over a period of 6 weeks (4). Therefore, FGF-21 was assumed to be a novel target with potential antidiabetic properties, which might be useful in the treatment of hyperglycemia, insulin resistance, and hyperlipidemia.However, human data did not directly support these assumptions, since increased serum FGF-21 levels were found in obese individuals, patients with type 2 diabetes, and subjects with metabolic syndrome (5,6). In addition FGF-21 levels correlated positively not only with adiposity but also with fasting insulin and triacylglycerols (5). A recent study (3) reported a significant increase of FGF-21 levels during prolonged fasting. This process appeared to be peroxisome proliferator–activator receptor (PPAR) α–dependent (2,3), although exact mechanisms leading to fasting-induced FGF-21 elevations are yet unknown.Various data support that metabolic parameters themselves can modulate the circulating levels of hormones and adipokines (7–10). Thus, free fatty acids (FFAs) activate PPARs and were found to be elevated in fasting conditions. We therefore speculated that FFAs themselves might regulate FGF-21. This hypothesis is supported by recent data demonstrating that FGF-21 levels are positively associated with FFAs (11) and triacylglycerols (3) in a cross-sectional study population of nondiabetic individuals. Although the direction of that relation is unclear in a cross-sectional study, it offers a potential mechanism linking starvation to the increased levels of FGF-21. We therefore investigated the effect of fatty acids on FGF-21 secretion in HepG2 cells in vitro. Based on these in vitro data, we performed a randomized controlled trial to explore whether an increase in circulating FFAs and triacylglycerols modifies FGF-21 levels in humans. Since an increase of FFAs is known to induce insulin resistance and hyperinsulinemia, the effect of insulin on FGF-21 was additionally investigated by performing a hyperinsulinemic-euglycemic clamp at baseline of a noncontrolled, rosiglitazone intervention trial. As some recent animal data (12) also suggested a PPARγ-dependent regulation of FGF-21, we finally evaluated the effect of the PPARγ agonist, rosiglitazone, in that human trial.     

Research knowledge among the participants in the Treatment for Adolescents With Depression Study (TADS)

OBJECTIVE: We examined the extent to which parents and adolescents participating in the Treatment for Adolescents With Depression Study (TADS) understood key aspects of the study. METHOD: TADS was a clinical trial comparing the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), their combination, and placebo in 439 adolescents (12-17 years old) with major depressive disorder. Six weeks after starting treatment, adolescents and their parents were asked to complete a questionnaire about critical elements of the trial. RESULTS: Completion rate was 67.2% for adolescents (N = 295) and 73.6% for parents (N = 323). More than 90% of the completers knew of the main purpose of the trial, possible assignment to placebo, and their right to withdraw participation at any time. However, about one third overall (and 49% in the CBT group) described TADS as "education" rather than "research." Of 12 questions, the mean number of correct answers was 10.3 (SD 1.7) among adolescents and 11.2 (SD 1.2) among parents (p <.0001). The most frequently stated reason for TADS participation was the pursuit of high-quality care. CONCLUSIONS: Most parents and adolescents were well-informed research participants. Difficulties in appreciating the research nature of the trial, however, emerged, especially among participants assigned to psychotherapy. Parents were overall better informed than adolescents.     

Cognitive-behavioral therapy for adolescent depression: a meta-analytic investigation of changes in effect-size estimates

OBJECTIVE: To explicate differences between early and recent meta-analytic estimates of the effects of cognitive-behavioral therapy (CBT) for adolescent depression. METHOD: Meta-analytic procedures were used to investigate whether methodological characteristics moderated mean effect sizes among 11 randomized, controlled trials of CBT focusing on adolescents meeting diagnostic criteria for unipolar depression. RESULTS: Cumulative meta-analyses indicated that effects of CBT have decreased from large effects in early trials, and confidence intervals have become narrower. Effect sizes were significantly smaller among studies that used intent-to-treat analytic strategies, compared CBT to active treatments, were conducted in clinical settings, and featured greater methodological rigor based on CONSORT (Consolidated Standards of Reporting Trials) criteria. The mean posttreatment effect size of 0.53 was statistically significant. CONCLUSIONS: Differences in estimates of the efficacy of CBT for depressed adolescents may stem from methodological differences between early and more recent investigations. Overall, results support the effectiveness of CBT for the treatment of adolescent depression.     

Ethinylestradiol differentially interferes with IGF-I in liver and extrahepatic sites during development of male and female bony fish

Growth and sexual development are closely interlinked in fish; however, no reports exist on potential effects of estrogen on the GH/IGF-I-axis in developing fish. We investigate whether estrogen exposure during early development affects growth and the IGF-I system, both at the systemic and tissue level. Tilapia were fed from 10 to 40 days post fertilization (DPF) with 17alpha-ethinylestradiol (EE(2)). At 50, 75, 90, and 165 DPF, length, weight, sex ratio, serum IGF-I (RIA), pituitary GH mRNA and IGF-I, and estrogen receptor alpha (ERalpha) mRNA in liver, gonads, brain, and gills (real-time PCR) were determined and the results correlated to those of in situ hybridization for IGF-I. Developmental exposure to EE(2) had persistent effects on sex ratio and growth. Serum IGF-I, hepatic IGF-I mRNA, and the number of IGF-I mRNA-containing hepatocytes were significantly decreased at 75 DPF, while liver ERalpha mRNA was significantly induced. At 75 DPF, a transient decline of IGF-I mRNA and a largely reduced number of IGF-I mRNA-containing neurons were observed in the female brain. In both sexes, pituitary GH mRNA was significantly suppressed. A transient downregulation of IGF-I mRNA occurred in ovaries (75 DPF) and testes (90 DPF). In agreement, in situ hybridization revealed less IGF-I mRNA signals in granulosa and germ cells. Our results show for the first time that developmental estrogen treatment impairs GH/IGF-I expression in fish, and that the effects persist. These long-lasting effects both seem to be exerted indirectly via inhibition of pituitary GH and directly by suppression of local IGF-I in organ-specific cells.     

How preferential is the preferential encoding of threatening stimuli? Working memory biases in specific anxiety and the Attentional Blink

Temporal visual working memory (VWM) biases in spider anxiety were studied with an Attentional Blink paradigm. In Experiment 1, participants viewed pictures sequentially presented at rates of 80 ms and were instructed to memorize two target pictures. We varied time between targets and valence of the second target (neutral: mushroom, positive: blossom, negative: spider). In Experiment 2, spider fearfuls and non-anxious controls (both without snake anxiety) participated. Here we tested two negative targets: disorder-related spiders and disorder-irrelevant snakes. Both positive and negative items were memorized more successfully than neutral targets. Spiders were preferentially recalled by spider fearfuls compared to non-anxious controls, implying temporal VWM biases in spider anxiety. This advantage for threat was not related to a disruption of the encoding of non-threatening targets presented before the threat item.     

Altered electrocortical brain activity after ACL reconstruction during force control

Afferent proprioceptive information from the knee joint may be altered due to a reconstruction of the anterior cruciate ligament (ACL), which could result in changes of cortical activity. The aim of the study is to look if force sensation and cortical activation measured by EEG are influenced by an ACL‐reconstruction when performing a force reproduction task. Nine patients after ACL reconstruction and nine healthy controls were asked to reproduce 50% of their maximal voluntary isometric contraction (MVIC) reproduction. EEG power values related to frequency bands and the error in reproduction were collected while performing the force reproduction. The aberration error demonstrated no significant differences between groups. The cortical activity results in significant higher frontal Theta power during the force reproduction task with the reconstructed limb (F3 and Fz: p < 0.05) of the ACL group compared to the controls. The EEG was able to measure changes in electrocortical activity after ACL‐reconstruction in force reproduction, whereas performance data was not affected. The results were discussed in terms of differences in attentional control with involvement of the anterior cingulate cortex related to higher frontal Theta power in the ACL patients. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1383–1389, 2011     

Eine niederdeutsche Aufzeichnung über die Kennzeichen der Lepra (c. 1400)

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