Outcome after surgical treatment of symptomatic delayed unions and nonunions of midshaft clavicle fractures

Introduction: Nonoperative treatment of displaced midshaft clavicle fractures is associated with higher nonunion rate than previously reported. Moreover, its occurrence can compromise shoulder function. The aim of this study was to evaluate the outcome of surgical treatment of symptomatic clavicle midshaft delayed and nonunion. Methods: Between 1999 and 2008, 19 clavicle delayed unions and nonunions were treated by open reduction and reconstructive plate fixation with augmentation by autologous bone graft. Iliac bone graft was used in 15 atrophic cases, and graft from the callus was used in 4 hypertrophic nonunions. There were 14 men and 5 women, with an average age of 41 years (range, 19 to 59 years) at time of surgery. No patient had undergone a previous surgery and all complained of shoulder pain. Delayed unions and nonunions were defined as non-healing after 3 and 6 months respectively. The mean time to surgery was 8 months (range, 4 to 23 months). All patients were pre and postoperatively clinically evaluated and imaged with standard radiographs until complete healing. Results: After a mean time of 3 months (range, 2 to 7 months) all fractures were completely healed. All patients reported full range of motion at time of last follow-up. Nine patients (47%) reported slight shoulder pain but all returned to their previous professional activities after a mean time of 3 months (range, 1 to 8 months). We reported 12 (63%) minor complications. There were 6 (32%) plate-related discomforts which resolved after hardware removal, two (11%) scar numbness, two (11%) adhesive capsulitis with spontaneous complete recovery, and two (11%) AC-joint pain treated successfully with local corticosteroids injection. Conclusion: Surgical treatment of delayed unions and nonunions of midshaft clavicle fractures yields satisfactory results and a high union rate. However, 50% of the patients may still complain of slight residual shoulder pain.

Regulation of the immune response by macrophage migration inhibitory factor: biological and structural features.

The classical T cell cytokine macrophage migration inhibitory factor (MIF) has reemerged recently as a critical mediator of the host immune and stress response. MIF has been found to be a mediator of several diseases including gram-negative septic shock and delayed-type hypersensitivity reactions. Its immunological functions include the modulation of the host macrophage and T and B cell response. In contrast to other known cytokines, MIF production is induced rather than suppressed by glucocorticoids, and MIF has been found to override the immunosuppressive effects of glucocorticoids. Recently, elucidation of the three-dimensional structure of MIF revealed that MIF has a novel, unique cytokine structure. Here the biological role of MIF is reviewed in view of its distinct immunological and structural properties.

Reconciliation of metabolites and biochemical reactions for metabolic networks.

Genome-scale metabolic network reconstructions are now routinely used in the study of metabolic pathways, their evolution and design. The development of such reconstructions involves the integration of information on reactions and metabolites from the scientific literature as well as public databases and existing genome-scale metabolic models. The reconciliation of discrepancies between data from these sources generally requires significant manual curation, which constitutes a major obstacle in efforts to develop and apply genome-scale metabolic network reconstructions. In this work, we discuss some of the major difficulties encountered in the mapping and reconciliation of metabolic resources and review three recent initiatives that aim to accelerate this process, namely BKM-react, MetRxn and MNXref (presented in this article). Each of these resources provides a pre-compiled reconciliation of many of the most commonly used metabolic resources. By reducing the time required for manual curation of metabolite and reaction discrepancies, these resources aim to accelerate the development and application of high-quality genome-scale metabolic network reconstructions and models.

Delayed diagnosis of acute ischemic stroke in children - a registry-based study in Switzerland.

QUESTIONS UNDER STUDY/PRINCIPLES: After arterial ischemic stroke (AIS) an early diagnosis helps preserve treatment options that are no longer available later. Paediatric AIS is difficult to diagnose and often the time to diagnosis exceeds the time window of 6 hours defined for thrombolysis in adults. We investigated the delay from the onset of symptoms to AIS diagnosis in children and potential contributing factors. METHODS: We included children with AIS below 16 years from the population-based Swiss Neuropaediatric Stroke Registry (2000-2006). We evaluated the time between initial medical evaluation for stroke signs/symptoms and diagnosis, risk factors, co-morbidities and imaging findings. RESULTS: A total of 91 children (61 boys), with a median age of 5.3 years (range: 0.2-16.2), were included. The time to diagnosis (by neuro-imaging) was <6 hours in 32 (35%), 6-12 hours in 23 (25%), 12-24 hours in 15 (16%) and >24 hours in 21 (23%) children. Of 74 children not hospitalised when the stroke occurred, 42% had adequate outpatient management. Delays in diagnosis were attributed to: parents/caregivers (n = 20), physicians of first referral (n = 5) and tertiary care hospitals (n = 8). A co-morbidity hindered timely diagnosis in eight children. No other factors were associated with delay to diagnosis. A total of 17 children were inpatients at AIS onset. CONCLUSIONS: One-third of children with AIS were diagnosed within six hours. Diagnostic delay was predominately caused by insufficient recognition of stroke symptoms. Increased public and expert awareness and immediate access to diagnostic imaging are essential. The ability of parents/caregivers and health professionals to recognise stroke symptoms in a child needs to be improved.

Neural control of vascular reactions: impact of emotion and attention.

This study investigated the neural regions involved in blood pressure reactions to negative stimuli and their possible modulation by attention. Twenty-four healthy human subjects (11 females; age = 24.75 ± 2.49 years) participated in an affective perceptual load task that manipulated attention to negative/neutral distractor pictures. fMRI data were collected simultaneously with continuous recording of peripheral arterial blood pressure. A parametric modulation analysis examined the impact of attention and emotion on the relation between neural activation and blood pressure reactivity during the task. When attention was available for processing the distractor pictures, negative pictures resulted in behavioral interference, neural activation in brain regions previously related to emotion, a transient decrease of blood pressure, and a positive correlation between blood pressure response and activation in a network including prefrontal and parietal regions, the amygdala, caudate, and mid-brain. These effects were modulated by attention; behavioral and neural responses to highly negative distractor pictures (compared with neutral pictures) were smaller or diminished, as was the negative blood pressure response when the central task involved high perceptual load. Furthermore, comparing high and low load revealed enhanced activation in frontoparietal regions implicated in attention control. Our results fit theories emphasizing the role of attention in the control of behavioral and neural reactions to irrelevant emotional distracting information. Our findings furthermore extend the function of attention to the control of autonomous reactions associated with negative emotions by showing altered blood pressure reactions to emotional stimuli, the latter being of potential clinical relevance.

Delayed-Choice Experiments and the Metaphysics of Entanglement

Delayed-choice experiments in quantum mechanics are often taken to undermine a realistic interpretation of the quantum state. More specifically, Healey has recently argued that the phenomenon of delayed-choice entanglement swapping is incompatible with the view that entanglement is a physical relation between quantum systems. This paper argues against these claims. It first reviews two paradigmatic delayed-choice experiments and analyzes their metaphysical implications. It then applies the results of this analysis to the case of entanglement swapping, showing that such experiments pose no threat to realism about entanglement.

Pharmacovigilance in pregnancy: adverse drug reactions associated with fetal disorders.

Abstract Objective: To provide the first update on drug safety profiles and adverse drug reactions (ADRs) associated with fetal disorders from the Swiss national ADR database. Methods: We conducted a retrospective study using data from 202 pharmacovigilance reports on drug-associated fetal disorders from the Swiss national ADR database from 1990 to 2009. Evaluated aspects included administrative information on the report, drug exposure, and disorders. Results: The ADR reporting frequency on the topic of fetal disorders has increased during the last 20 years, from only 1 report in 1991 to a maximum of 31 reports in 2008. Nervous system drugs were the most frequently reported drug group (40.2%) above all antidepressants and antiepileptics. The highest level of overall drug intake could be observed for the 1st trimester (85.4%), especially for the first 6 weeks of pregnancy. The most frequently reported types of fetal disorders were malformations (68.8%), especially those of the musculoskeletal and circulatory systems. A positive association was discovered between antiepileptics and malformations in general and in particular of the circulatory system and the eye, ear, face, and neck. Conclusions: The results suggest that the nervous system drug group bears an especially high risk for malformations. The most commonly identified drug exposures can help focus pharmacoepidemiologic efforts in drug-induced birth defects.

Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death.

Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. During excitotoxicity neuronal mitochondria are fragmented, but the mechanism underlying this process is poorly understood. Here, we show that Mfn2 is the only member of the mitochondrial fusion/fission machinery whose expression is reduced in in vitro and in vivo models of excitotoxicity. Whereas in cortical primary cultures, Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation in an early phase that can be reversed once the insult has ceased, Mfn2 downregulation intervenes in a delayed mitochondrial fragmentation phase that progresses even when the insult has ceased. Downregulation of Mfn2 causes mitochondrial dysfunction, altered calcium homeostasis, and enhanced Bax translocation to mitochondria, resulting in delayed neuronal death. We found that transcription factor MEF2 regulates basal Mfn2 expression in neurons and that excitotoxicity-dependent degradation of MEF2 causes Mfn2 downregulation. Thus, Mfn2 reduction is a late event in excitotoxicity and its targeting may help to reduce excitotoxic damage and increase the currently short therapeutic window in stroke.

Adverse reactions to biologic agents and their medical management.

Biologic agents have substantially advanced the treatment of immunological disorders, including chronic inflammatory and autoimmune diseases. However, these drugs are often associated with adverse events (AEs), including allergic, immunological and other unwanted reactions. AEs can affect almost any organ or system in the body and can occur immediately, within minutes to hours, or with a delay of several days or more after initiation of biologic therapy. Although some AEs are a direct consequence of the functional inhibition of biologic-agent-targeted antigens, the pathogenesis of other AEs results from a drug-induced imbalance of the immune system, intermediary factors and cofactors, a complexity that complicates their prediction. Herein, we review the AEs associated with biologic therapy most relevant to rheumatic and immunological diseases, and discuss their underlying pathogenesis. We also include our recommendations for the medical management of such AEs. Increased understanding and improved risk management of AEs induced by biologic agents will enable better use of these versatile immune-response modifiers.

Age and adverse drug reactions from psychopharmacological treatment: Data from the AMSP drug surveillance programme in Switzerland.

QUESTION UNDER STUDY: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years. METHODS: Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP. RESULTS: A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions. CONCLUSION: The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

Parental post-traumatic reactions after premature birth: implications for sleeping and eating problems in the infant.

BACKGROUND: Progress in perinatal medicine has made it possible to increase the survival of very or extremely low birthweight infants. Developmental outcomes of surviving preterm infants have been analysed at the paediatric, neurological, cognitive, and behavioural levels, and a series of perinatal and environmental risk factors have been identified. The threat to the child's survival and invasive medical procedures can be very traumatic for the parents. Few empirical reports have considered post-traumatic stress reactions of the parents as a possible variable affecting a child's outcome. Some studies have described sleeping and eating problems as related to prematurity; these problems are especially critical for the parents. OBJECTIVE: To examine the effects of post-traumatic reactions of the parents on sleeping and eating problems of the children. DESIGN: Fifty families with a premature infant (25-33 gestation weeks) and a control group of 25 families with a full term infant participated in the study. Perinatal risks were evaluated during the hospital stay. Mothers and fathers were interviewed when their children were 18 months old about the child's problems and filled in a perinatal post-traumatic stress disorder questionnaire (PPQ). RESULTS: The severity of the perinatal risks only partly predicts a child's problems. Independently of the perinatal risks, the intensity of the post-traumatic reactions of the parents is an important predictor of these problems. CONCLUSIONS: These findings suggest that the parental response to premature birth mediates the risks of later adverse outcomes. Preventive intervention should be promoted.