Major complications occurred in 35% of 3-column osteotomies and at similar rates for both PSO (38%) and VCR (22%) procedures. The presence of a major complication did not affect the ultimate clinical outcomes at 2 years or more.

Next-generation sequencing (NGS) has emerged as a powerful technique for the detection of genetic variants in the clinical laboratory. NGS can be performed using DNA from FFPE tissue, but it is unknown whether such specimens are truly equivalent to unfixed tissue for NGS applications. To address this question, we performed hybridization-capture enrichment and multiplexed Illumina NGS for 27 cancerrelated genes using DNA from 16 paired fresh-frozen and routine FFPE lung adenocarcinoma specimens and conducted extensive comparisons between the sequence data from each sample type. This analysis revealed small but detectable differences between FFPE and frozen samples. Compared with frozen samples, NGS data from FFPE samples had smaller library insert sizes, greater coverage variability, and an increase in C to T transitions that was most pronounced at CpG dinucleotides, suggesting interplay between DNA methylation and formalin-induced changes; however, the error rate, library complexity, enrichment performance, and coverage statistics were not significantly different. Comparison of base calls between paired samples demonstrated concordances of >99.99%, with 96.8% agreement in the single-nucleotide variants detected and >98% accuracy of NGS data when compared with genotypes from an orthogonal single-nucleotide polymorphism array platform. This study demonstrates that routine processing of FFPE samples has a detectable but negligible effect on NGS data and that these samples can be a reliable substrate for clinical NGS testing. Next-generation sequencing (NGS) has recently emerged as a cost-effective method for identifying clinically actionable genetic variants across many genes in a single test. This approach has now been successfully applied to detect somatic mutations in hematopoietic malignant tumors, solid tumors, and constitutional mutations in genes associated with inherited cancer predisposition syndromes, among other clinical testing applications. 1e5 Further, numerous studies have demonstrated that NGS techniques are able to detect the full range of DNA variation, including single-nucleotide variants (SNVs), insertions/deletions, translocations, and copy number changes, 4,6e11 in the research setting. Thus, clinical NGS-based diagnostics offer an improvement over current molecular methods, such as PCR and Sanger sequencing, by which only a limited spectrum of mutations can be identified at a single genomic locus.Implementing NGS methods for routine clinical testing requires validation across the range of variables encountered in a clinical diagnostics laboratory, including the various specimen types that may be submitted for testing. The preferred specimen for most molecular tests is fresh tissue (eg, blood anticoagulated with EDTA or fresh tissue from a surgical biopsy or excision in saline) because this minimizes processing and Supported by the

Context.— Perinatal death is an increasingly important problem as the COVID-19 pandemic continues, but the mechanism of death has been unclear. Objective.— To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for SARS-CoV-2. Design.— Case-based retrospective clinico-pathological analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.— All 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis, the three findings constituting SARS-CoV-2 placentitis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25/68) and chronic villitis (32%; 22/68). The majority (19, 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.— The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

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