Chromosome alignment at the equator of the mitotic spindle is a highly conserved step during cell division; however, its importance to genomic stability and cellular fitness is not understood. Normal mammalian somatic cells lacking KIF18A function complete cell division without aligning chromosomes. These alignment-deficient cells display normal chromosome copy numbers in vitro and in vivo, suggesting that chromosome alignment is largely dispensable for maintenance of euploidy. However, we find that loss of chromosome alignment leads to interchromosomal compaction defects during anaphase, abnormal organization of chromosomes into a single nucleus at mitotic exit, and the formation of micronuclei in vitro and in vivo. These defects slow cell proliferation and are associated with impaired postnatal growth and survival in mice. Our studies support a model in which the alignment of mitotic chromosomes promotes proper organization of chromosomes into a single nucleus and continued proliferation by ensuring that chromosomes segregate as a compact mass during anaphase.

Intraoperative PTH assay has added a new dimension to primary and revision parathyroid surgery. It is cost-effective and accurate and may reduce the morbidity of surgical intervention in revision procedures.

SUMMARYChromosome alignment at the equator of the mitotic spindle is a highly conserved step during cell division, however, its importance to genomic stability and cellular fitness are not understood. Normal mammalian somatic cells lacking Kif18A function complete cell division without aligning chromosomes. These alignment-deficient cells display normal chromosome copy numbers in vitro and in vivo, suggesting that chromosome alignment is largely dispensable for maintenance of euploidy. However, we find that loss of chromosome alignment leads to interchromosomal compaction defects during anaphase, abnormal organization of chromosomes into a single nucleus at mitotic exit, and the formation of micronuclei in vitro and in vivo. These defects slow cell proliferation and reduce postnatal growth and survival with variable penetrance in mice. Our studies support a model in which the alignment of mitotic chromosomes promotes proper nuclear envelope reassembly and continued proliferation by ensuring that chromosomes segregate as a compact mass during anaphase.

Fluorescent in situ hybridization has become an essential tool for diagnosing and monitoring hematological disease. Testing for minimal residual disease requires precise and accurate normal cut-offs. There is no consensus in the field on the correct method of establishing a normal reference range. We discuss and compare several proposed statistical methods to calculate normal reference ranges, including Gaussian statistics, the beta inverse function, and a binomial treatment of the data. We demonstrate that a binomial treatment of the data is an accurate and simple method to calculate a normal reference range.

Severe traumatic brain injury is one of the leading causes of death and disability in the United States. The initial management of traumatic brain injury involves early resuscitation, computed tomography scanning, and surgical evacuation of mass lesions, when indicated. Recent research suggests that the prevention and treatment of secondary brain injury decrease mortality and improve outcomes. Specifically, treatment should address not only cerebral protection but also prevention of injury to other organ systems. To achieve the best outcomes, attention must be focused on optimizing blood pressure and brain tissue oxygenation, maintaining adequate cerebral perfusion pressures, and preventing seizures. In addition, maximizing good outcomes depends on proactively addressing the risk of common sequelae of brain injury, including infection, deep venous thrombosis, and inadequate nutrition. Guidelines developed for the management of severe traumatic brain injury have dramatically improved functional neurological outcomes.

We report the second case of ETV6-ACSL6 associated myeloproliferative neoplasm that has received a full course of imatinib therapy. The patient was a 51-year-old previously healthy man who presented with three months of worsening dyspnea and was found to have a white count of 216,000/cmm, of which 84% were eosinophil lineage. Cytogenetic analysis revealed a t(5;12)(q31~33;p13). FISH was negative for PDGFRB rearrangement but additional FISH testing demonstrated an ACSL6 rearrangement. ETV6-ACSL6 gene fusion is a rare abnormality that most often presents as a myeloproliferative-type disorder with prominent eosinophilia or basophilia. Review of the literature yielded a total of 11 previous cases. This gene fusion results in a t(5;12)(q31~33;p13) that mimics the t(5;12) found in ETV6-PDGFRB neoplasms. Identification of the fusion genes involved in t(5;12) in eosinophilia-associated myeloproliferative disorders is crucial to direct an effective treatment plan. In particular, while tyrosine kinase inhibitor therapy is effective in patients with PDGFRB rearrangement, there is little information on imatinib efficacy in patients with ETV6-ACSL6 gene fusion. Our patient was found to be nonresponsive to imatinib therapy.

Cytogenetic analysis demonstrated abnormal karyotypes in nearly half of this series of mesenchymal neoplasms, the majority of which consisted of recognized aberrations reported in the literature.

Context.-The College of American Pathologists published guideline recommending bone marrow synoptic reporting for hematologic neoplasms.Objective.-To evaluate the impact of pathology-driven algorithmic testing (PDAT) with integrated reporting for bone marrow examination on test utilization, ability to render a specific World Health Organization diagnosis, and clinician satisfaction 1 year after implementation.Design.-We reviewed the hematopathology reports, integrated synoptic reports, and ancillary test results generated during a 12-month period. The initial diagnosis from the hematopathology report was compared with the final diagnosis on the integrated synoptic reports. Test utilization data were compared with a previous year in which ancillary testing was ordered at clinician discretion. Clinicians were anonymously surveyed to assess their satisfaction with PDAT and integrated reporting.