Pain during the first year after scoliosis surgery in adolescents, an exploratory, prospective cohort study

Objective: Approximately 50% of adolescents who have undergone scoliosis surgery still experience severe pain one year postoperatively. We explored the postoperative pain trajectory and the potential value of preoperative Thermal Quantitative Sensory Testing (T-QST) as predictor of chronic postsurgical pain after scoliosis surgery. Design: Single-center prospective cohort study in adolescents undergoing scoliosis surgery. Outcomes: Prevalence of chronic postsurgical pain (CPSP) one year after scoliosis surgery and postsurgical pain course during this year. The need for rescue medication and the relationship between pre-operative T-QST, acute pain and CPSP. Results: Thirty-nine patients (mean age 13.9 years; SD 1.9 years) completed the study. One year postoperatively, ten patients (26%) self-reported pain [numeric rating scale (NRS) score ≥ 4]) when moving and two (5%) when in rest. Four of these patients (10.3%) experienced neuropathic pain. The pre-operative cold pain threshold was lower (p = 0.002) in patients with CPSP at 12 months. Preoperative cold and heat pain thresholds were correlated with the number of moderate or severe pain reports (NRS ≥ 4) in the first week postoperatively (r -.426; p = 0.009 and r.392; p = 0.016, respectively). Conclusions: One year after scoliosis surgery, a significant part of patients (26%) still reported pain, some with neuropathic characteristics. Better diagnosis and treatment is needed; our study suggests that T-QST could be further explored to better understand and treat children with this negative outcome.</p

Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring

Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease. © 2015 The American Society of Human Genetics

Pain during the first year after scoliosis surgery in adolescents, an exploratory, prospective cohort study

Objective: Approximately 50% of adolescents who have undergone scoliosis surgery still experience severe pain one year postoperatively. We explored the postoperative pain trajectory and the potential value of preoperative Thermal Quantitative Sensory Testing (T-QST) as predictor of chronic postsurgical pain after scoliosis surgery. Design: Single-center prospective cohort study in adolescents undergoing scoliosis surgery. Outcomes: Prevalence of chronic postsurgical pain (CPSP) one year after scoliosis surgery and postsurgical pain course during this year. The need for rescue medication and the relationship between pre-operative T-QST, acute pain and CPSP. Results: Thirty-nine patients (mean age 13.9 years; SD 1.9 years) completed the study. One year postoperatively, ten patients (26%) self-reported pain [numeric rating scale (NRS) score ≥ 4]) when moving and two (5%) when in rest. Four of these patients (10.3%) experienced neuropathic pain. The pre-operative cold pain threshold was lower (p = 0.002) in patients with CPSP at 12 months. Preoperative cold and heat pain thresholds were correlated with the number of moderate or severe pain reports (NRS ≥ 4) in the first week postoperatively (r -.426; p = 0.009 and r.392; p = 0.016, respectively). Conclusions: One year after scoliosis surgery, a significant part of patients (26%) still reported pain, some with neuropathic characteristics. Better diagnosis and treatment is needed; our study suggests that T-QST could be further explored to better understand and treat children with this negative outcome.</p

Non-culprit MACE-rate in LRP:The influence of optimal medical therapy using DAPT and statins

Background/Purpose: The Lipid Rich Plaque (LRP) study demonstrated the association between coronary plaque lipid content and outcomes. In this LRP substudy, we assessed the impact of optimal medical therapy (OMT) on the occurrence of non-culprit major adverse cardiac events (NC-MACE). Advanced intracoronary imaging modalities are able to identify patients with vulnerable coronary lesion morphology associated with future events. Methods/Materials: A total of 1270 patients who underwent cardiac catheterization for suspected coronary artery disease (CAD) with evaluable maxLCBI4mm in non-culprit vessels and known medical therapy after discharge were followed for 2 years. OMT was defined as the use of a statin and dual antiplatelet therapy (DAPT). Results: Among the 1270 patients included in this substudy, 1110 (87.7%) had PCI for an index event, and 1014 (80%) patients received OMT. Estimated cumulative incidence functions of NC-MACE did not differ significantly between patients treated with or without OMT (log-rank p-value = 0.876). In patients labeled high risk (maxLCBI4mm > 400), cumulative incidence function also did not differ between patients treated with vs without OMT (log-rank p-value = 0.19). Conclusions: In the current LRP analysis, we could not identify a beneficial effect of OMT in the reduction of NC-MACE rate, even in patients with high-risk plaques during 24-month follow-up

Accurate detection of circulating tumor DNA using nanopore consensus sequencing

Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ~60×, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in clinical workflows

Author Correction: Accurate detection of circulating tumor DNA using nanopore consensus sequencing

The Data Availability statement in the original version of the paper reads: “The sequencing datasets generated during the current study are available upon request at EGA, under accession number EGAS00001003759”. However, as this data upload was not successful, the authors reuploaded the data under a different accession number and have amended the Data Availability statement to read “The sequencing datasets generated during the current study are available upon request at EGA, under accession number EGAS00001007090”. The original article has been corrected.</p

Long-term clinical outcomes of everolimus-eluting bioresorbable scaffolds versus everolimus-eluting stents:final five-year results of the AIDA randomised clinical trial

Background: Absorb bioresorbable vascular scaffold (BVS)-related events have been reported between 1 and 3 years – the period of active scaffold bioresorption. Data on the performance of the Absorb BVS in daily clinical practice beyond this time point are scarce. Aims: This report aimed to provide the final five-year clinical follow-up of the Absorb BVS in comparison with the XIENCE everolimus-eluting stent (EES). In addition, we evaluated the effect of prolonged dual antiplatelet therapy (DAPT) administration on events in the scaffold group. Methods: AIDA was a multicentre, investigator-initiated, non-inferiority trial, in which 1,845 unselected patients with coronary artery disease were randomly assigned to either the Absorb BVS (n=924) or the XIENCE EES (n=921). Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction or target vessel revascularisation, was the primary endpoint. Scaffold thrombosis cases were matched with controls and tested for the effect of prolonged DAPT. Results: Up to five-year follow-up, there was no difference in TVF between the Absorb BVS (17.7%) and the XIENCE EES (16.1%) (hazard ratio [HR] 1.31, 95% confidence interval [CI]: 0.90-1.41; p=0.302). Definite or probable device thrombosis (DT) occurred in 43 patients (4.8%) in the scaffold group compared to 13 patients (1.5%) in the stent group (HR 3.32, 95% CI: 1.78-6.17; p<0.001). DT between 3 and 4 years occurred six times in the Absorb arm versus three times in the XIENCE arm. Between 4 and 5 years, the incidence was three versus two, respectively. Of those three DT in the scaffold group, two occurred in XIENCE EES-treated lesions. The odds ratio of scaffold thrombosis in patients on DAPT compared to off DAPT throughout five-year follow-up was 0.36 (95% CI: 0.15-0.86). Conclusions: The excess risk of the Absorb BVS on late adverse events, in particular device thrombosis, in routine PCI continues up to 4 years and seems to plateau afterwards

Probabilistic (logic) programming concepts

A multitude of different probabilistic programming languages exists today, all extending a traditional programming language with primitives to support modeling of complex, structured probability distributions. Each of these languages employs its own probabilistic primitives, and comes with a particular syntax, semantics and inference procedure. This makes it hard to understand the underlying programming concepts and appreciate the differences between the different languages. To obtain a better understanding of probabilistic programming, we identify a number of core programming concepts underlying the primitives used by various probabilistic languages, discuss the execution mechanisms that they require and use these to position and survey state-of-the-art probabilistic languages and their implementation. While doing so, we focus on probabilistic extensions of logic programming languages such as Prolog, which have been considered for over 20 years