Outcomes of Revision Surgery Following Instrumented Posterolateral Fusion in Degenerative Lumbar Spinal Stenosis: A Comparative Analysis between Pseudarthrosis and Adjacent Segment Disease

Study DesignRetrospective study.PurposeWe examined the clinical and radiological outcomes of patients who received revision surgery for pseudarthrosis or adjacent segment disease (ASD) following decompression and instrumented posterolateral fusion (PLF).Overview of LiteratureAt present, information regarding the outcomes of revision surgery for complications such as pseudarthrosis and ASD following instrumented PLF is limited.MethodsThis study examined 60 patients who received PLF for degenerative lumbar spinal stenosis and subsequently developed pseudarthrosis or ASD leading to revision surgery. Subjects were divided into a group of 21 patients who received revision surgery for pseudarthrosis (Group P) and a group of 39 patients who received revision surgery for ASD (Group A). Clinical outcomes were evaluated using the visual analogue scales for back pain (VAS-BP) and leg pain (VAS-LP), the Korean Oswestry disability index (K-ODI), and each patient's subjective satisfaction. Radiological outcomes were evaluated from the extent of bone union, and complications in the two groups were compared.ResultsVAS-LP at final follow-up was not statistically different between the two groups (p =0.353), although VAS-BP and K-ODI at final follow-up were significantly worse in Group P than in Group A (all p <0.05), and only 52% of the patients in Group P felt that their overall well-being had improved following revision surgery. Fusion rates after the first revision surgery were 71% (15/21) in Group P and 95% (37/39) in Group A (p =0.018). The rate of reoperation was significantly higher in Group P (29%) than in Group A (5%) (p =0.021) due to complications.ConclusionsClinical and radiological outcomes were worse in patients who had received revision surgery for pseudarthrosis than in those who had revision surgery for ASD. Elderly patients should be carefully advised of the risks and benefits before planning revision surgery for pseudarthrosis

Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement

Background: Craniosynostosis (CRS) is a premature closure of calvarial sutures caused by gene mutation or environmental factors or interaction between the two. Only a small proportion of non-syndromic CRS (NSC) patients have a known genetic cause, and thus, it would be meaningful to search for a causative gene disruption for the development NSC. We applied a whole genome sequencing approach on a 15-month-old boy with sagittal and metopic synostosis to identify a gene responsible for the development of the disease. Methods and results Conventional chromosome study revealed a complex paracentric inversion involving 2q14.3 and 2q34. Array comparative genomic hybridisation did not show any copy number variation. Multicolour banding analysis was carried out and the breakpoints were refined to 2q14 and 2q34. An intronic break of the PTH2R gene was detected by whole genome sequencing and fluorescence in situ hybridisation analysis confirmed disruption of PTH2R. Conclusions: We report PTH2R as a gene that is disrupted in NSC. The disruption of the PTH2R gene may cause uncontrolled proliferation and differentiation of chondrocytes, which in turn results in premature closure of sutures. This addition of PTH2R to the list of genes associated with NSC expands our understanding of the development of NSC

PI3K-Akt-Wnt Pathway Is Implicated in Exercise-Induced Improvement of Short-term Memory in Cerebral Palsy Rats

Purpose Maternal lipopolysaccharide (LPS) injection induces neurodevelopmental disorders, such as cerebral palsy. Exercise activates phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway that enhances neurogenesis. Wnt ligands are also implicated in the hippocampal neurogenesis and synaptic plasticity. Glycogen synthase kinase-3β (GSK-3β) is a downstream molecule of Akt, and GSK-3β is known to modulate hippocampal neurogenesis negatively. Methods Cerebral palsy was made by maternal LPS-injection. On the 5 weeks after birth, treadmill running was applied to the rat pups of the exercise groups, for 30 minutes, 5 times a week during 6 weeks. Results Treadmill running alleviated short-term memory impairments of the cerebral palsy rat pups. Hippocampal cell proliferation was increased and hippocampal apoptosis was suppressed by treadmill running in the cerebral palsy rat pups. Hippocampal phosphorylated-PI3K/PI3K ratio, phosphorylated-Akt/Akt ratio, and Wnt expression were enhanced by treadmill running in the cerebral palsy rat pups. In contrast, hippocampal phosphorylated-GSK-3β/GSK-3β ratio and β-catenin expression were suppressed by treadmill running in the cerebral palsy rat pups. Conclusions The results of this study showed that short-term memory improvement due to treadmill running in cerebral palsy occurs via activation of the PI3K-Akt-Wnt pathway

Genetic diagnosis of inborn errors of immunity using clinical exome sequencing

Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK, UNC13D, STAT3, IL2RG, IL10RA, NRAS, SH2D1A, GATA2, TET2, PRF1, and UBA1, of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2, and UBA1. In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments