Preoperative Narcotic Use, Impaired Ambulation Status, and Increased Intraoperative Blood Loss Are Independent Risk Factors for Complications Following Posterior Cervical Laminectomy and Fusion Surgery.

ObjectiveThis retrospective cohort study seeks to identify risk factors associated with complications following posterior cervical laminectomy and fusion (PCLF) surgery.MethodsAdults undergoing PCLF from 2012 through 2018 at a single center were identified. Demographic and radiographic data, surgical characteristics, and complication rates were compared. Multivariate logistic regression models identified independent predictors of complications following surgery.ResultsA total of 196 patients met the inclusion criteria and were included in the study. The medical, surgical, and overall complication rates were 10.2%, 23.0%, and 29.1% respectively. Risk factors associated with medical complications in multivariate analysis included impaired ambulation status (odds ratio [OR], 2.27; p=0.02) and estimated blood loss over 500 mL (OR, 3.67; p=0.02). Multivariate analysis revealed preoperative narcotic use (OR, 2.43; p=0.02) and operative time (OR, 1.005; p=0.03) as risk factors for surgical complication, whereas antidepressant use was a protective factor (OR, 0.21; p=0.01). Overall complication was associated with preoperative narcotic use (OR, 1.97; p=0.04) and higher intraoperative blood loss (OR, 1.0007; p=0.03).ConclusionPreoperative narcotic use and estimated blood loss predicted the incidence of complications following PCLF for CSM. Ambulation status was a significant predictor of the development of a medical complication specifically. These results may help surgeons in counseling patients who may be at increased risk of complication following surgery

Preoperative Narcotic Use, Impaired Ambulation Status, and Increased Intraoperative Blood Loss Are Independent Risk Factors for Complications Following Posterior Cervical Laminectomy and Fusion Surgery.

ObjectiveThis retrospective cohort study seeks to identify risk factors associated with complications following posterior cervical laminectomy and fusion (PCLF) surgery.MethodsAdults undergoing PCLF from 2012 through 2018 at a single center were identified. Demographic and radiographic data, surgical characteristics, and complication rates were compared. Multivariate logistic regression models identified independent predictors of complications following surgery.ResultsA total of 196 patients met the inclusion criteria and were included in the study. The medical, surgical, and overall complication rates were 10.2%, 23.0%, and 29.1% respectively. Risk factors associated with medical complications in multivariate analysis included impaired ambulation status (odds ratio [OR], 2.27; p=0.02) and estimated blood loss over 500 mL (OR, 3.67; p=0.02). Multivariate analysis revealed preoperative narcotic use (OR, 2.43; p=0.02) and operative time (OR, 1.005; p=0.03) as risk factors for surgical complication, whereas antidepressant use was a protective factor (OR, 0.21; p=0.01). Overall complication was associated with preoperative narcotic use (OR, 1.97; p=0.04) and higher intraoperative blood loss (OR, 1.0007; p=0.03).ConclusionPreoperative narcotic use and estimated blood loss predicted the incidence of complications following PCLF for CSM. Ambulation status was a significant predictor of the development of a medical complication specifically. These results may help surgeons in counseling patients who may be at increased risk of complication following surgery

Correction to: An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids (Genetics in Medicine, (2021), 23, 4, (740-750), 10.1038/s41436-020-01027-3)

In the original author list, Seth Perlman’s degrees were listed as MD, PhD. Dr Perlman’s degree is MD. The original version has been corrected

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

Purpose We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1 beta subunit of the cyclic AMP-dependent protein kinase A (PKA). Methods Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development. Results Recent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C>T (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs. Conclusion Our study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder

An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids

Purpose: In this study we investigate the disease etiology in 12 patients with de novo variants in FAR1 all resulting in an amino acid change at position 480 (p.Arg480Cys/His/Leu). Methods: Following next-generation sequencing and clinical phenotyping, functional characterization was performed in patients’ fibroblasts using FAR1 enzyme analysis, FAR1 immunoblotting/immunofluorescence, and lipidomics. Results: All patients had spastic paraparesis and bilateral congenital/juvenile cataracts, in most combined with speech and gross motor developmental delay and truncal hypotonia. FAR1 deficiency caused by biallelic variants results in defective ether lipid synthesis and plasmalogen deficiency. In contrast, patients’ fibroblasts with the de novo FAR1 variants showed elevated plasmalogen levels. Further functional studies in fibroblasts showed that these variants cause a disruption of the plasmalogen-dependent feedback regulation of FAR1 protein levels leading to uncontrolled ether lipid production. Conclusion: Heterozygous de novo variants affecting the Arg480 residue of FAR1 lead to an autosomal dominant disorder with a different disease mechanism than that of recessive FAR1 deficiency and a diametrically opposed biochemical phenotype. Our findings show that for patients with spastic paraparesis and bilateral cataracts, FAR1 should be considered as a candidate gene and added to gene panels for hereditary spastic paraplegia, cerebral palsy, and juvenile cataracts