The Differences Between Same-Day and Staged (Circumferential) Fusion Surgery in Adult Spinal Deformity: Protocol for a Systematic Review.

BACKGROUND: Adult spinal deformity (ASD) is a deformity in the curvature of the adult spine. ASD includes a range of pathology that leads to decreased quality of life for patients as well as debilitating morbidities. Treatment can range from nonoperative management to long-segment surgical corrections and depends greatly on the deformity and patient profiles. If surgical treatment is indicated, circumferential (a combined anterior and posterior approach) fusion is one of the tools in the spine surgeon's armamentarium. Depending on the complexity, the procedure is either completed on the same day or staged. Determining whether to perform a circumferential surgery in a staged fashion is based largely on the surgeon's preference and perception of the individual case complexity; at present, there is no high-quality evidence that can be used to support that decision. OBJECTIVE: This paper presents the protocol for a systematic review that aims to investigate the differences between same-day versus staged circumferential fusion surgery in ASD both in patient selection and in outcomes. METHODS: Searches will be performed on MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. Gray literature and the reference lists of articles included in the full-text screening will also be screened for inclusion. Results will be exported to Covidence. Data will be collected on demographics, type of procedures performed, surgery levels, blood loss, total operation time, length of stay, disposition, readmissions (30 days and 90 days), and perioperative complications. Patient-reported outcomes will also be assessed. Data quality assessment of randomized controlled trials will be performed using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials, and nonrandomized studies will be assessed with the ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) tool. All screening, quality assessment, and data extraction will be done by 2 independent reviewers. A descriptive synthesis will be performed, and data will be evaluated for further analysis. RESULTS: This study is currently in the screening phase. There are no results yet. The search strategy has been developed and documented. Information has been exported to Covidence. Upon conclusion of the critical appraisal stage, screening and extraction, as well as a synthesis of the results, will be performed. CONCLUSIONS: The intended review will summarize the differences in perioperative outcomes and complications between same-day and staged (circumferential) fusion surgery in adult spinal deformity. It will also describe the patients selected for such procedures based on their demographics and pathology. Identified gaps in knowledge will provide insight into current limitations and guide further studies on this topic. TRIAL REGISTRATION: PROSPERO CRD42022339764; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339764. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/42331.

PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans.

Intracranial aneurysm (IA) rupture leads to subarachnoid hemorrhage, a sudden-onset disease that often causes death or severe disability. Although genome-wide association studies have identified common genetic variants that increase IA risk moderately, the contribution of variants with large effect remains poorly defined. Using whole-exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4, encoding peptidyl-prolyl cis-trans isomerase-like 4, in both familial and index IA cases. Ppil4 depletion in vertebrate models causes intracerebral hemorrhage, defects in cerebrovascular morphology and impaired Wnt signaling. Wild-type, but not IA-mutant, PPIL4 potentiates Wnt signaling by binding JMJD6, a known angiogenesis regulator and Wnt activator. These findings identify a novel PPIL4-dependent Wnt signaling mechanism involved in brain-specific angiogenesis and maintenance of cerebrovascular integrity and implicate PPIL4 gene mutations in the pathogenesis of IA.

Evaluation of Lumbar Spine Bracing as a Postoperative Adjunct to Single-level Posterior Lumbar Spine Surgery.

BACKGROUND: Clinical practice in postoperative bracing after posterior single-level lumbar spine fusion (PLF) is inconsistent between providers. This study seeks to assess the effect of bracing on short-term outcomes related to safety, quality of care, and direct costs. METHODS: Retrospective cohort analyses of consecutive patients undergoing single-level PLF with or without bracing at a three-hospital urban academic medical center (2013-2017) were undertaken (n = 906). Patient demographics and comorbidities were analyzed. Test of independence, Mann-Whitney-Wilcoxon test, and logistic regression were used to assess differences in length of stay (LOS), discharge disposition/need for postacute care, quality-adjusted life year (QALY), surgical site infection (SSI), hospital cost, total cost, readmission within 30 days, and emergency room (ER) visits within 30 days. RESULTS: Among the study population, 863 patients were braced and 43 were not braced. No difference was seen between the two groups in short-term outcomes from surgery including LOS (P = 0.836), discharge disposition (P = 0.226), readmission (P = 1.000), ER visits (P = 0.281), SSI (P = 1.000), and QALY gain (P = 0.319). However, the braced group incurred a significantly higher direct hospital cost (median increase of 41.43%, P < 0.001) compared to the unbraced cohort (bracing cost excluded). There was no difference in graft type (P = 0.145) or comorbidities (P = 0.20-1.00) such as obesity (P = 1.000), smoking (P = 1.000), chronic obstructive pulmonary disease (P = 1.000), hypertension (P = 0.805), coronary artery disease (P = 1.000), congestive heart failure (P = 1.000), and total number of comorbidities (P = 0.228). CONCLUSION: Short-term data suggest that removal of bracing from the postoperative regimen for PLF will not result in increased adverse outcomes but will reduce cost.

Recessive LAMC3 mutations cause malformations of occipital cortical development.

The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations.

Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations.

The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.