Safety, effectiveness and predictors for early reoperation in therapeutic and prophylactic vertebroplasty: short-term results of a prospective case series of patients with osteoporotic vertebral fractures

Abstract Introduction Vertebroplasty (VP) is a cost-efficient alternative to kyphoplasty; however, regarding safety and vertebral body (VB) height restoration, it is considered inferior. We assessed the safety and efficacy of VP in alleviating pain, improving quality of life (QoL) and restoring alignment. Methods In a prospective monocenter case series from May 2007 until July 2008, there were 1,408 vertebroplasties performed during 319 interventions in 306 patients with traumatic, lytic and osteoporotic fractures. The 249 interventions in 233 patients performed because of osteoporotic vertebral fractures were analyzed regarding demographics, treatment and radiographic details, pain alleviation (VAS), QoL improvement (NASS and EQ-5D), complications and predictors for new fractures requiring a reoperation. Results The osteoporotic patient sample consisted of 76.7% (179) females with a median age of 80 years. A total of 54 males had a median age of 77 years. On average, there were 1.8 VBs fractured and 5 VBs treated. The preoperative pain was assessed by the visual analog scale (VAS) and decreased from 54.9 to 40.4 pts after 2 months and 31.2 pts after 6 months. Accordingly, the QoL on the EQ-5D measure (−0.6 to 1) improved from 0.35 pts before surgery to 0.56 pts after 2 and to 0.68 pts after 6 months. The preoperative Beck Index (anterior height/posterior height) improved from a mean of 0.64 preoperative to 0.76 postoperative, remained stable at 2 months and slightly deteriorated to 0.72 at 6 months postoperatively. There were cement leakages in 26% of the fractured VBs and in 1.4% of the prophylactically cemented VBs; there were symptoms in 4.3%, and most of them were temporary hypotension and one pulmonary cement embolism that remained asymptomatic. The univariate regression model revealed a tendency for a reduced risk for new or refractures on radiographs (OR = 2.61, 95% CI 0.92–7.38, p = 0.12) and reoperations (OR = 2.9, 95% CI 0.94–8.949, p = 0.1) when prophylactic augmentation was performed. The final multivariate regression model revealed male patients to have an about three times higher refracture risk (radiographic) (OR = 2.78, p = 0.02) at 6 months after surgery. Patients with a lumbar index fracture had an about three to five times higher refracture/reoperation risk than patients with a thoracic (OR = 0.33/0.35, p = 0.009/0.01) or thoracolumbar (OR = 0.32/0.22, p = 0.099/0.01) index fracture. Conclusion If routinely used, VP is a safe and efficacious treatment option for osteoporotic vertebral fractures with regard to pain relief and improvement of the QoL. Even segmental realignment can be partially achieved with proper patient positioning. Certain patient or fracture characteristics increase the risk for early radiographic refractures or new fractures, or a reoperation; a consequent prophylactic augmentation showed protective tendencies, but the study was underpowered for a final conclusion.

Interactions between short-term and long-term plasticity: shooting for a moving target

Far from being static transmission units, synapses are highly dynamical elements that change over multiple time scales depending on the history of the neural activity of both the pre- and postsynaptic neuron. Moreover, synaptic changes on different time scales interact: long-term plasticity (LTP) can modify the properties of short-term plasticity (STP) in the same synapse. Most existing theories of synaptic plasticity focus on only one of these time scales (either STP or LTP or late-LTP) and the theoretical principles underlying their interactions are thus largely unknown. Here we develop a normative model of synaptic plasticity that combines both STP and LTP and predicts specific patterns for their interactions. Recently, it has been proposed that STP arranges for the local postsynaptic membrane potential at a synapse to behave as an optimal estimator of the presynaptic membrane potential based on the incoming spikes. Here we generalize this approach by considering an optimal estimator of a non-linear function of the membrane potential and the long-term synaptic efficacy—which itself may be subject to change on a slower time scale. We find that an increase in the long-term synaptic efficacy necessitates changes in the dynamics of STP. More precisely, for a realistic non-linear function to be estimated, our model predicts that after the induction of LTP, causing long-term synaptic efficacy to increase, a depressing synapse should become even more depressing. That is, in a protocol using trains of presynaptic stimuli, as the initial EPSP becomes stronger due to LTP, subsequent EPSPs should become weakened and this weakening should be more pronounced with LTP. This form of redistribution of synaptic efficacies agrees well with electrophysiological data on synapses connecting layer 5 pyramidal neurons.

Short-Term Effects of Social Exclusion at work and Worries on Sleep

The present study investigated short-term effects of daily social exclusion at work on various indicators of sleep quality and tested the mediating role of work-related worries using a time-based diary study with ambulatory assessments of sleep quality. Ninety full-time employees participated in a 2-week data collection. Multilevel analyses revealed that daily workplace social exclusion and work-related worries were positively related to sleep fragmentation in the following night. Daily social exclusion, however, was unrelated to sleep onset latency, sleep efficiency and self-reported sleep quality. Moreover, worries did not mediate the effect of social exclusion at work on sleep fragmentation. Theoretical and practical implications of the results are discussed.

Predictors of sickness absence in patients with a new episode of low back pain in primary care

This study examines predictors of sickness absence in patients presenting to a health practitioner with acute/ subacute low back pain (LBP). Aims of this study were to identify baseline-variables that detect patients with a new LBP episode at risk of sickness absence and to identify prognostic models for sickness absence at different time points after initial presentation. Prospective cohort study investigating 310 patients presenting to a health practitioner with a new episode of LBP at baseline, three-, six-, twelve-week and six-month follow-up, addressing work-related, psychological and biomedical factors. Multivariate logistic regression analysis was performed to identify baseline-predictors of sickness absence at different time points. Prognostic models comprised 'job control', 'depression' and 'functional limitation' as predictive baseline-factors of sickness absence at three and six-week follow-up with 'job control' being the best single predictor (OR 0.47; 95%CI 0.26-0.87). The six-week model explained 47% of variance of sickness absence at six-week follow-up (p<0.001). The prediction of sickness absence beyond six-weeks is limited, and health practitioners should re-assess patients at six weeks, especially if they have previously been identified as at risk of sickness absence. This would allow timely intervention with measures designed to reduce the likelihood of prolonged sickness absence.

Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2) and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D) patients that are more prone to develop insulin resistance, including: i) acute post-prandial hyperlipidemic challenge (n=10), ii) 4 days of high-fat (HF) or high-fat/high-protein (HFHP) (n=10), iii) 7 (HFruc1, n=16) or 6 (HFruc2, n=9) days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF) PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL) and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1). Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05) in healthy volunteers and by 34% (p=0.001) in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p<0.0001) in young healthy male volunteers. Spearman’s correlations revealed that plasma PCSK9 concentrations upon 7-day HFruc1 diet were positively associated with plasma triglycerides (r=0.54, p=0.01) and IHCL (r=0.56, p=0.001), and inversely correlated with hepatic (r=0.54, p=0.014) and whole-body (r=−0.59, p=0.0065) insulin sensitivity. Conclusions Plasma PCSK9 concentrations vary minimally in response to a short term high-fat diet and they are not accompanied with changes in cholesterolemia upon high-fructose diet. Short-term high-fructose intake increased plasma PCSK9 levels, independent on cholesterol synthesis, suggesting a regulation independent of SREBP-2. Upon this diet, PCSK9 is associated with insulin resistance, hepatic steatosis and plasma triglycerides.

Predictors of short term treatment outcome in patients with achalasia following endoscopic or surgical therapy

Pneumatic balloon dilation and surgical myotomy are the most effective treatments for achalasia. While there is controversy which method is best, the aim of the current study was to identify predictors of symptom recurrence after endoscopic or surgical therapy.

Short-term preoperative supplementation of an immunoenriched diet does not improve clinical outcome in well-nourished patients undergoing abdominal cancer surgery

A recent study suggested that the anti-inflammatory effect of immunonutrition starts after only two d. We therefore investigated the effect of an immunoenriched oral diet administered for three d preoperatively.